Search Results Within Category "Digestive Systems & Liver Disease"
A Longitudinal Observational Study of the Natural History and Management of Patients With HCC
TARGET-HCC is a longitudinal, observational study of patients being managed for HCC in usual clinical practice. TARGET-HCC will create a research registry of participants with HCC within academic and community real-world practices in order to assess the safety and effectiveness of the entire spectrum of current and future therapies across diverse populations.
Call 214-648-5005
studyfinder@utsouthwestern.edu
• Male or female patients, age ≥18 years
• Patients with a histological/cytological or radiological diagnosis of HCC (mixed HCC cholangiocarcinoma may be included; patients who are candidates for surgical and non-surgical treatment, as well as those being followed without specific HCC therapy may be included)
• Inability to provide written informed consent
A Longitudinal Observational Study of Patients With Nonalcoholic Steatohepatitis (NASH) and Related Conditions Across the Entire Spectrum of Nonalcoholic Fatty Liver Disease (NAFLD)
TARGET-NASH is a longitudinal observational cohort study of patients being managed for NASH and related conditions across the entire spectrum NAFLD in usual clinical practice. TARGET-NASH is a research registry of patients with NAFL or NASH within academic and community real-world practices maintained in order to assess the safety and effectiveness of current and future therapies.
Call 214-648-5005
studyfinder@utsouthwestern.edu, maurice.turk@childrens.com
• Adults and children (age 2 or older) being managed or treated for nonalcoholic fatty liver disease. Diagnosis is based on the clinical judgement of the care provider.
• Inability to provide informed assent/consent.
Stereotactic Radiosurgery (SRS) Dose-Escalation Study for Brain Metastasis (SRS)
SRS dose escalation for brain metastases in radiation-naïve patients will establish true tolerable doses, which may exceed the current standard doses. This may lead to an improvement in local control, patient survival, and/or quality-of life.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
• Biopsy-proven non-hematopoietic malignancy, except for small cell lung cancer, germ cell cancer, or unknown primary tumor.
• Radiographic evidence by MRI (or by CT scan with CT contrast if ineligible or intolerant of MRI) of brain metastasis. (If patient is unable to tolerate MRI contrast, an MRI without contrast is acceptable if lesions are visible)
• All brain metastases must be outside the brain stem (midbrain, pons and medulla).
• Patient must have 10 or less brain metastases.
• The maximum diameter of any lesion must be less than or equal to 3.0 cm.
• Previous treatment with surgery, radiation, chemotherapy, immunotherapy or any targeted agents are allowed provided that:
• Radiation was not to the brain.
• Surgery to the brain was > 7 days prior to SRS and there remains at least one additional brain metastasis that can be targeted with SRS
• Age ≥ 18 years.
• ECOG Performance Score of 2 or better/Karnofsky Performance Status score of 50-60 or better.
• All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Ability to understand and the willingness to sign a written informed consent. Exclusion Criteria
• Patients had craniotomy and surgery to the brain within 7 days from the date of SRS.
• Patients with leptomeningeal metastasis. NOTE: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive CSF cytology and/or equivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology, unless a parenchymal lesion can adequately explain the neurologic symptoms and/or signs. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In that patient, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion.
• Patients with a contraindication to both MRI (with or without contrast) and CT scan (with contrast)
• Patients with life expectancy < 3 months.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Subjects must not be pregnant or nursing at the time of SRS treatment due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
Phase 1 Dose-escalating Study of MM-398 (Irinotecan Sucrosofate Liposome Injection) Plus Intravenous Cyclophosphamide in Recurrent or Refractory Pediatric Solid Tumors
This is a Phase 1 study of the combination of two drugs: MM-398 and Cyclophosphamide. The goal is to find the highest dose of MM-398 that can be given safely when it is used together with the chemotherapy drug Cyclophosphamide.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
• Histologically or cytologically-confirmed Ewing sarcoma, rhabdomyosarcoma, neuroblastoma, or osteosarcoma
• Disease progression after prior therapy in locally advanced or metastatic setting
• Measurable or evaluable disease based on the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria
• Age 12 months to <21 years
• Adequate bone marrow reserves, hepatic function, and renal function
• Recovered from effects of any prior surgery or cancer therapy
• Patients 18 years or older will provide written consent. A parent or legal guardian of a patient <18 years of age will provide informed consent and patients 11 to 18 years of age will provide written assent or as per participating institutional policy.
• Clinically significant gastrointestinal disorders
• NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure
• Active infection or unexplained fever
• Known hypersensitivity to any of the components of MM-398 or other liposomal products
• Recent Investigational therapy
• Pregnant or breast feeding; females of child-bearing potential must test negative for pregnancy at the time of enrollment
Alcoholic Hepatitis Network Observational Study
The purpose of this research study is to create a clinical database and bio-repository. To do this, we will obtain blood, urine, and stool samples (e.g., biological samples) and personal health information from you to use in future research studies related to alcoholic hepatitis or other diseases. Part of your blood sample will be used to extract your DNA. DNA is the genetic material that gives us unique characteristics. We are doing this research study because we are trying to find out more about how and why illnesses related to alcoholic hepatitis or other diseases occur in people. To do this, we will study the biological samples and personal health information from healthy and sick people. A "biological sample" is usually blood, but can be any body fluid. "Personal Health Information" includes such items as your name, age, gender, race, and/or your medical information. It can also include data from measurements and tests that you had while participating in another research study or that were done during the course of your regular medical care or doctor visits.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Leticia.Rodriguez@UTSouthwestern.edu
• A clinical diagnosis of alcoholic hepatitis
• Serum total bilirubin >3 mg/dL
• Subject or guardian ability to understand and willingness to provide written consent
• Age greater or equal to 21 years
• Re-enrolment of an alcoholic hepatitis donor is permissible up to 4 times if the donor presents with a new episode of alcoholic hepatitis 24 weeks or longer after the most recent enrolment in the study Exclusion criteria
• Liver disease significantly caused by hemochromatosis, autoimmune liver disease, Wilson disease, NAFLD, and acute viral hepatitis
• (NOTE: The presence of chronic hepatitis C, hepatitis B, or HIV is not exclusion to participation.)Pregnant or breast feeding Based on the judgment of the investigator, subject is not capable of understanding or complying with the study requirements. CONTROLS: Heavy drinkers without significant liver disease Inclusion criteria
• History of chronic alcohol consumption sufficient to cause liver damage. Generally, this is considered to be >40 g/day or >280g/week on average for women and >60 g/day or >420 g/week on average for men, for many years (usually decades). Judgement about chronic alcohol consumption will be made by the site investigator.
• Subject or guardian ability to understand and willingness to provide written consent
• Age greater or equal to 21 years Exclusion criteria
• Past evidence of alcoholic liver disease, defined as a bilirubin > 2.0 mg/dL, an AST >
• 5 ULN, and any hospital admission for liver disease, or the presence of esophageal varices or ascites (at any time in the past).
• Liver disease significantly caused by hemochromatosis, autoimmune liver disease, Wilson disease, NAFLD, and acute viral hepatitis (NOTE: The presence of chronic hepatitis C, hepatitis B, or HIV is not exclusion to participation.)
• Alcohol intake at less than 40 g/day or 280g/week on average for women and 60 g/day or 420 g/week on average for men for longer than the past 28 days
• If liver stiffness has been assessed within the prior 90 days, then stiffness suggesting fibrosis of F1 or greater is excluded. For Fibroscan, this is a fibrosis score >7.0 kPa.
• Pregnant or breast feeding
• Any of the following laboratory abnormalities within 90 days prior to signing the consent.
• Total bilirubin: >ULN*
• INR: > 1.4 5 *Individuals with a diagnosis of Gilbert's can have total bilirubin up to 3.0 mg/dL and still be eligible for participation. Healthy Controls Inclusion criteria
• AUDIT-C scores of <4 for men and <3 for women (signifying no alcohol misuse)
• Abstinent (consumption of less than one standard drink/week) during the 6 months prior to enrolment
• Ability to understand and willingness to provide written consent. Exclusion criteria
• Clinical history or laboratory evidence of liver disease including alcoholic liver disease, NAFLD, hemochromatosis, alcoholic hepatitis, autoimmune liver disease, Wilson disease, hepatitis C, or hepatitis B.
• Presence of diabetes (requiring treatment with oral agents or insulin).
• Significant heart disease (prior history of heart disease, other than hypertension)
• Chronic lung disease (requiring chronic treatment)
• Immune related conditions (such as Crohn's disease, rheumatoid arthritis, ulcerative colitis, systemic lupus erythematosus, severe psoriasis, etc.)
• Known infection with HIV
• Presumed infection, or use of antibiotics or other medications (e.g., corticosteroids) that would affect immune function, within the past 14 days
• BMI>35
• Current or known history of cancer (except in situ carcinoma of the cervix or adequately treated basal or squamous cell carcinoma of the skin) within 5 years prior to enrollment
• Pregnant or breast feeding
• Any of the following laboratory abnormalities within 90 days prior to signing the consent.
• Hemoglobin: <10 g/dL
• Conjugated bilirubin: > ULN
• INR: > 1.4
• AST: >40 IU/mL
• ALT: >40 IU/mL
• Based on the judgment of the investigator, subject is not capable of complying with the study requirements
ENhancing Recovery in CHildren Undergoing Surgery (ENRICH-US)
Initiated in the 1990s, perioperative Enhanced Recovery Protocols (ERPs) have progressively gained traction in a wide range of adult surgical disciplines and have decreased hospital length of stay (LOS), in-hospital costs, complications, and result in a markedly improved patient care experience that mitigates the physiologic stress of surgery and hastens recovery. Implementation of ERPs in pediatric surgery is lagging and concerted efforts to demonstrate both clinical effectiveness and to examine obstacles to implementation are needed. Specifically, pediatric patients with inflammatory bowel disease (IBD) undergoing elective abdominal surgery represent an ideal population in which to study the implementation of ERPs. Almost one third of patients with Crohn's disease (CD) and a quarter of patients with Ulcerative Colitis (UC) present before age 20. Up to three-quarters of CD patients require GI surgery for medically refractory disease and all patients with UC require colectomy to either manage severe disease or to mitigate cancer risks. Over the past four years, investigators modified existing adult ERPs to meet the needs of pediatric patients undergoing elective GI surgery. Based on the positive results of a pilot study, the investigators propose to conduct a multicenter, prospective, pragmatic, study using a stepped-wedge, cluster, randomized controlled trial design to evaluate the effectiveness of ERPs while assessing implementation fidelity, sustainability, and site-specific adaptations. The cluster randomized trial design is ideally suited for this type of pragmatic intervention implementation. The National Implementation Research Network's five Active Implementation Frameworks (AIFs), which identifies competency, organization, and leadership as drivers of implementation, empowers team collaboration, and facilitates rapid-cycle evaluation, will be used to optimize implementation. The investigators propose to conduct the ENhancing Recovery In CHildren Undergoing Surgery (ENRICH-US) Study in 18 US hospitals participating in the Pediatric Surgical Research Collaborative (PedSRC) by implementing and evaluating the effectiveness of the Pediatric ERP in GI Surgery on clinical outcomes for pediatric IBD patients and by measuring by fidelity and sustainability of the intervention while identifying organizational, leadership, and competency-based drivers of improved ERP implementation and sustainability.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Maria.ValenciaBradd@UTSouthwestern.edu
• Pediatric patients ages 10-18
• Clinical diagnosis of Inflammatory Bowel Disease (Crohn's Disease or Ulcerative Colitis)
• Undergoing elective gastrointestinal/colorectal surgical procedures
• Children undergoing emergent/urgent gastrointestinal/colorectal surgical procedures
• Patients/families who cannot read and write English or Spanish
Linerixibat Long-term Safety and Tolerability Study
This is an open-label, non-comparator, global, multi-center, long-term safety study for evaluating safety and tolerability of linerixibat in participants with cholestatic pruritus in primary biliary cholangitis (PBC) who participated in a prior eligible clinical trial with linerixibat. Participants will be administered with 90 milligrams (mg) linerixibat orally twice daily. The total daily dose will not exceed 180 mg total daily dose. The effect of linerixibat on measures of quality of life and health-related quality of life in the study population will also be assessed. The duration of the study will be approximately four years until study end and the total duration of study participation will vary by participant depending upon time of entry relative to study end in their respective country. Approximately 75 participants will be enrolled in this study.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Uchenna.Agwunobi@UTSouthwestern.edu
• Participant must be 18 to 80 years of age inclusive, at the time of signing the informed consent in the participant's parent trial BAT117213 (NCT01899703) or 201000 (NCT02966834)
• Participants with a diagnosis of PBC and a history of associated pruritus as evidenced by randomization into a prior eligible linerixibat clinical trial.
• Participants must have completed the main treatment period in a prior eligible linerixibat clinical trial.
• Male or female; Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Contraception by male participants or male partners of female participants is not required in this protocol.
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
• is not a woman of childbearing potential (WOCBP) or
• is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1 percent [%] per year), with low user dependency, as described during the intervention period and for at least 4 weeks, after the last dose of study intervention. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention;
• a WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention;
• if a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
• The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
• Capable of giving signed informed consent as described in which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Screening total bilirubin >2x upper limit of normal (ULN). Total bilirubin >2x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%.
• Screening ALT or AST >6x ULN.
• Screening eGFR <45 milliliters per minute per 1.73 square meter (mL/min/1.73m^2) based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
• History or presence of hepatic decompensation (e.g., variceal bleeds, encephalopathy or ascites).
• Presence of actively replicating viral hepatitis B or C (HBV, HCV) infection and/or confirmed hepatocellular carcinoma or biliary cancer.
• Recent or current clinically significant diarrhea in the Investigator's medical opinion.
• Current symptomatic cholelithiasis or inflammatory gallbladder disease is exclusionary. Participants with history of cholecystectomy >=3 months before screening may be eligible for enrollment.
• Current diagnosis or previous diagnosis of colorectal cancer.
• Any current medical condition (e.g. psychiatric disorder, senility or dementia), which may affect the participant's ability to comply with the protocol specified procedures.
• Use of Obeticholic acid: within 8 weeks prior to the date of the screening visit and may not restart until after the end of the study or study withdrawal.
• Administration of any other ileal bile acid transporter (IBAT) inhibitor in the 1 month prior to screening.
• Current enrollment or participation in any other clinical study (except for 201000) involving an investigational study treatment within 8 weeks prior to the screening visit.
• QT interval corrected (QTc) >480 millisecond (msec): A QTc >480 msec (12-lead electrocardiogram [ECG]) at screening is exclusionary.
• History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (~240 milliliter [mL]) of beer, 1 glass (125 mL) of wine or 1 measure (25 mL) of spirits.
Study to Investigate the Efficacy and Safety of Dupilumab in Pediatric Patients With Active Eosinophilic Esophagitis (EoE) (EoE KIDS)
The Primary objective is to demonstrate the efficacy of dupilumab treatment compared with placebo in pediatric patients with active eosinophilic esophagitis (EoE) based on histologic improvement meeting validated histologic criteria. The Secondary objectives are: - To demonstrate the efficacy of dupilumab compared to placebo in pediatric patients with active EoE after 16 weeks of treatment as assessed by endoscopic visual measurements of disease activity using the Eosinophilic Esophagitis-Endoscopic Reference Score (EoE-EREFS) and histologic abnormalities as measured by the EoE Histology Scoring System (EoE-HSS) - To evaluate the safety, tolerability, and immunogenicity of dupilumab treatment for up to 16 weeks in pediatric patients with active EoE - To evaluate the effects of dupilumab on transcriptomic signatures associated with EoE and type 2 inflammation - To study the effects of dupilumab on the type 2 inflammation gene expression signature - To evaluate the concentration-time profile of functional dupilumab in serum in this population - To assess efficacy of long-term (52 weeks) dupilumab treatment - To assess safety, tolerability, and immunogenicity of long-term (52 weeks) dupilumab treatment - To evaluate the impact of dupilumab treatment on EoE signs and symptoms
Call 214-648-5005
studyfinder@utsouthwestern.edu, Kaylee.Lirely@Childrens.com
• A documented diagnosis of eosinophilic esophagitis (EoE)
• Baseline endoscopic biopsies with a demonstration on central reading of intraepithelial eosinophilic infiltration Key
• Body weight <5 kg or ≥60 kg at screening
• Other causes of esophageal eosinophilia
• Active Helicobacter pylori
• History of Crohn's disease, ulcerative colitis, celiac disease, or prior esophageal surgery
• Any esophageal stricture unable to be passed with a standard, diagnostic, upper endoscope or any critical esophageal stricture that requires dilation at screening
• Treatment with swallowed topical corticosteroids within 8 weeks prior to baseline standard of care endoscopy
• History of bleeding disorders or esophageal varices that, in the opinion of the investigator, would put the patient at undue risk for significant complications from an endoscopy procedure
• Active parasitic infection or suspected parasitic infection
• Known or suspected immunodeficiency disorder NOTE: Other protocol defined inclusion/exclusion criteria apply.
Effects of Hypoglossal Nerve Stimulation on Cognition and Language in Down Syndrome and Obstructive Sleep Apnea
This study is a prospective, single-arm study conducted under a common implant and follow-up protocol. The objective will be to follow fifty-seven (57) adolescents and young adults (10-21 years of age), with Down syndrome, moderate to severe sleep apnea, and post-adenotonsillectomy, for 12 months after undergoing implant of the Inspire Upper Airway Stimulation (UAS) System. The study is being conducted in order to evaluate objective change in cognition and expressive language after implant and therapy with the Inspire UAS System.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Francesca.Chambers@UTSouthwestern.edu
• Diagnosis of Down syndrome
• Age 10-21 years
• Prior adenotonsillectomy
• Severe OSA (AHI > 10, AHI < 50, no more than 25% AHI attributable to central events) based on prior in-lab PSG performed after adenotonsillectomy and within 18 months of enrollment
• Approval from at least two of the three physician reviewers based upon the results of a routine drug-induced sleep endoscopy (DISE) having occurred within 12 months of enrollment
• Subjects must have either tracheotomy or be ineffectively treated with CPAP due to non-compliance, discomfort, un-desirable side effects, persistent symptoms despite compliance use, or refusal to use the device
• Children and their parents/guardians must be willing to have stimulation hardware permanently implanted, and be willing to participate in follow-up visits, postoperative PSG, and questionnaire completion
• Children's parents/guardians must complete a questionnaire confirming that their child is capable of communicating feelings of pain or discomfort. They must also confirm they are able to assess their child for adverse effects related to device implantation
• Children and their parents/guardians must be proficient in English
• Body mass index (BMI) above the 95th percentile for subject's age
• Circumferential airway collapse at the level of the velopharynx observed during DISE
• Other medical conditions resulting in medical instability (eg. congestive heart failure, recent open heart surgery, immunosuppression, or chronic lung disease or aspiration)
• Presence of another medical condition requiring future magnetic resonance imaging (MRI) of the chest
• Patients with another implantable device which could interact unintentionally with the Inspire system
• Any contraindication for general anesthesia
• History of bleeding or clotting disorders and those on blood thinning or NSAID medications for the week prior to implantation surgery. Subjects will be asked to refrain from the use of NSAIDS for two weeks after implantation or any revision surgeries
• Subject is currently taking muscle relaxant medication
• Life expectancy less than 12 months
• Subject's inability to communicate pain or discomfort to their caretaker/parent, based on parental or investigator assessment
• Nonverbal candidates will be excluded due to an inability to complete testing procedures including expressive language sampling
• Subjects with a co-occurring diagnosis of autism spectrum disorder
• Subjects that have a positive β-HCG
• Subjects deemed unfit for participation by the investigator for any other reason
A Study to Assess the Efficacy, Safety, and Tolerability of Oral LPCN 1148 in Male Subjects With Cirrhosis of the Liver and Sarcopenia
This is a randomized, double-blind, placebo-controlled study to assess the efficacy, safety, and tolerability of LPCN 1148 in men with cirrhosis of the liver and sarcopenia.
Call 214-648-5005
studyfinder@utsouthwestern.edu, NAHID.ATTAR@UTSouthwestern.edu
• Male ≥ 18 years old
• Currently listed, on the liver transplant waitlist for cirrhosis secondary to Hepatitis B or C infection, Alcoholic Liver Disease (ALD), or Non-Alcoholic Steatohepatitis (NASH)
• Evidence of sarcopenia with appropriate cutoff recommended by clinical guidance
• Suspected or proven hepatocellular carcinoma (HCC)
• History of current or suspected prostate or breast cancer
• History of malignancies other than prostate, breast, or HCC, unless successfully treated with curative intent and believed to be cured (defined as complete remission lasting at least 5 years)
• History of uncontrolled or recurrent portal hypertensive bleeding, including uncontrolled or recurrent bleeding from varices, gastropathy, colopathy, or hemorrhoidal bleeding.
• History or current thrombosis (including portal vein thrombosis), thromboembolism, or treatment for portal vein thrombosis
• History of hemochromatosis
• History of hypercoagulable state (e.g. Factor V Leiden deficiency, protein C deficiency, protein S deficiency, anti-thrombin III deficiency, or the presence of lupus anticoagulant)
• Prior history of complications of ascites including:
• Spontaneous bacterial peritonitis
• Hepatic hydrothorax
• MELD score > 25
• Abnormal lab value in serum chemistry, hematology, or urinalysis that the PI considers clinically significant, including but not limited to:
• PSA > 4 ng/mL
• Polycythemia (Hematocrit >54%) or history of polycythemia
• ALT or AST > 5x ULN
• ALP > 1.5x ULN
• Platelet count < 30,000/mL
• EGFR < 60 mL/min/1.73 m2
• Total bilirubin > 3.0 mg/dL
• Serum albumin < 2.8 g/dL
• INR > 2.3 or PT prolongation > 6.0 seconds
• Subjects with PSA between 2.5 ng/mL and 4 ng/mL are excluded only if any of the below criteria are met at baseline:
• Hematocrit > 48%
• I-PSS > 19
• Any irregularity found on digital rectal examination of the prostate
• Subjects with PSA > 3 ng/mL are excluded only if any of the below criteria are met at baseline:
• Subject is African American
• Subject has a first-degree relative who has a history of prostate cancer
• Hematocrit > 48%
• I-PSS > 19
• Any irregularity found on digital rectal examination of the prostate
• Clinically significant abnormal prostate digital rectal examination (DRE) in the opinion of the PI, with DRE screening initiated at International Prostate Symptom Score (I-PSS) > 19
• History of bariatric surgery
• History of stroke or myocardial infarction within the past 5 years
• Known positivity for Human Immunodeficiency Virus (HIV) infection
• Acute liver failure as the indication for addition to the liver transplant waitlist
• Estimated life expectancy less than 3 months or expected to undergo liver transplant within 3 months
• Known heart failure of New York Heart Association class III or IV
• Evidence of severe encephalopathy or encephalopathy that is not controlled despite adequate medical therapy
• History of prior organ transplant
• History of Fontan physiology
• History of pulmonary embolus
• Porto-pulmonary hypertension
• Hepatopulmonary syndrome
• Uncontrolled epilepsy or migraine
• Active substance abuse or dependency extending to within the previous 6 months
• History of significant sensitivity or allergy to testosterone, or product excipients.
• Use of known strong inhibitors (e.g., ketoconazole) or inducers (e.g., dexamethasone, phenytoin, rifampin, carbamazepine) of cytochrome P450 3A (CYP3A) within 30 days prior to study drug administration and through the end of the study
• Subjects who are currently receiving any androgens (testosterone or other androgens or androgen-containing supplements) and are unwilling to washout prior to screening a. Washout: 12 weeks following long-acting intramuscular androgen injections; 4 weeks following topical or buccal androgens; 3 weeks following oral androgens
• Uncontrolled hypertension (>160/90 mmHg despite treatment)
• Uncontrolled obstructive sleep apnea
• Use of any investigational drug within 5 half-lives of the last dose or in the past 6 months prior to Study Day -2 without medical monitor and/or Sponsor approval
• Subject who is not willing to use adequate contraception for the duration of the study
• Any other condition, which in the opinion of the investigator would impede compliance to the study protocol (including diet, exercise, and alcohol abstinence) or hinder completion of the study
• Failure to give informed consent
Abatacept in Immune Checkpoint Inhibitor Myocarditis (ATRIUM)
The primary aim is to test whether abatacept, as compared to placebo, is associated with a reduction in major adverse cardiac events (MACE) among participants hospitalized with myocarditis secondary to an immune checkpoint inhibitor (ICI). The primary outcome, MACE, is a composite of first occurrence of cardiovascular death, non-fatal sudden cardiac arrest, cardiogenic shock, significant ventricular arrythmias, significant bradyarrythmias, or incident heart failure.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
• Must have provided informed consent in a manner approved by the Investigator's Institutional Review Board (IRB) prior to any study-related procedure being performed. If a participant is unable to provide informed consent due to his/her medical condition, the participant's legally authorized representative may consent on behalf of the study participant, as permitted by local law and institutional Standard Operating Procedures;
• Aged greater than or equal to 18 years at the time of informed consent;
• Recent use of an FDA-approved immune checkpoint inhibitor (ICI, defined as administered an immune checkpoint inhibitor ≤ 6 months of myocarditis diagnosis), alone or in combination with other cancer therapies (i.e. chemotherapy, radiation therapy or targeted therapy). The FDA-approved ICI could be given as part of a clinical trial but not in combination with a new investigational agent which may cause myocarditis;
• A diagnosis of myocarditis.
• Hospitalized at the time of randomization;
• On 1000 mg of solumedrol per day for myocarditis or with an intent to initiate 1000 mg of solumedrol per day for myocarditis within 24 hours of first administration of study drug;
• Serum evidence of ongoing myocardial injury: Serum evidence of ongoing myocardial injury will be defined as an institutional troponin (either conventional or high-sensitivity troponin I or T, using the standard institutional assay) with a value that is ≥5 times the upper limit of the reference standard normal for that institution. The troponin assay may be adjusted based on sex depending on institutional standards. This value of troponin of ≥5 times above the institutional upper limits of normal value must be noted within 10 days prior to potential randomization. The 10-day period can be in the outpatient or inpatient setting. For example, a participant with a troponin value that on one occasion was ≥5 times the upper limits of institutional normal in the 10-day window prior to potential randomization (whether in the inpatient or outpatient setting), but later decreases below that threshold, typically due to starting corticosteroids, would still be considered eligible;
• The following laboratory parameters, not older than 48 hours at the time of randomization, and measured as part of usual care:
• Total white blood cell (WBC) count >2,500/μl
• Absolute neutrophil count (ANC) >1,500/μL
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) <20 times the upper limit of the institutional normal ranges;
• Women of childbearing potential (i.e., not postmenopausal, or surgically sterilized) must have a negative highly sensitive urine or serum pregnancy test prior to randomization. Participating women of childbearing potential must be willing to consistently use effective methods of contraception from screening until at least 90 days after administration of the last dose of study drug. Participating men must also be willing to consistently use effective methods of contraception from screening until at least 90 days after administration of the last dose of study drug; and
• Must be willing and able to abide by all study requirements and restrictions.
• Must not have experienced any of the following (as defined in the section on the primary endpoint) in the 30-day period prior to randomization:
• A sudden cardiac arrest
• Cardiogenic shock as defined. A significant bradyarrhythmia (Mobitz type II second degree atrioventricular block or third degree (complete) atrio-ventricular (AV) block, for which an intervention with a temporary or permanent pacemaker is completed or recommended).
• A significant tachyarrhythmia (ventricular fibrillation of any duration or sustained ventricular tachycardia (>30 seconds, >120 beats per minute); or a ventricular tachyarrhythmia requiring intervention.
• Recent (≤2 month) exposure to abatacept or belatacept.
• Concurrent or recent (≤2 month) use of the following non-corticosteroid immunosuppressive therapies prior to randomization: mycophenolate, JAK STAT inhibitors (including but not limited to upadacitinib, tofacitinib, baricitinib, and filgotinib), tacrolimus, anti-thymocyte globulin, alemtuzumab, infliximab, and plasma exchange. The use of intravenous immunoglobulin is permitted prior to randomization and during study treatment.
• Currently enrolled in another interventional study utilizing systemic agents for the management of ICI-related toxicities.
• Female who is pregnant, breastfeeding, or is considering becoming pregnant during the study or for approximately 90 days after the last dose of study drug.
• Male who is considering fathering a child or donating sperm during the study or for approximately 30 days after the last dose of study drug.
• Any active, chronic, or recurrent viral infection that, based on the investigator's clinical assessment, makes the participant an unsuitable candidate for the study. These may include hepatitis B virus (HBV) or hepatitis C virus (HCV), recurrent or disseminated (even a single episode) herpes zoster, and disseminated (even a single episode) herpes simplex. Active HBV and HCV are defined as: HBV: hepatitis B surface antigen (HBs Ag) positive (+) or detected sensitivity on the HBV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) qualitative test for Hepatitis B core antibody (HBc Ab) positive (+) participants; HCV: HCV ribonucleic acid (RNA) detectable in any participant with anti-HCV antibody (HCV Ab). Patients with active Covid-19 infection will be excluded. This is defined as the period of ongoing symptoms in the setting of a positive Covid-19 test, or until 10 days after symptom onset and after resolution of fever for at least 24 hours, without the use of fever-reducing medications.
• Known active tuberculosis (TB), history of incompletely treated TB, suspected or known extrapulmonary TB, suspected or known systemic bacterial or fungal infections;
• Receipt of any live vaccine within four weeks prior to the first dose of study drug, or expected need of live vaccination during study participation including at least 90 days after the last dose of IV study drug.
• Any medical condition that could interfere with, or for which the treatment might interfere with, the conduct of the study or interpretation of the study results, or that would, in the opinion of the Investigator, increase the risk of the participant by participating in the study.
• Any factors that, in the Investigator's opinion, are likely to interfere with study procedures, such as history of noncompliance with scheduled appointments.