The SLIM LIVER Study
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the safety and tolerability of a drug called semaglutide and to see whether it can reduce IHTG. IHTG will be measured by magnetic resonance imaging (MRI; an MRI machine contains a powerful magnet that uses simple radio waves to take pictures of organs). Semaglutide (brand name Ozempic®) is a drug that is used to treat people who have diabetes; it also causes weight loss and may provide some protection against cardiovascular disease and diabetes. In PLWH, the use of semaglutide to reduce weight and the level of IHTG are experimental.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Single-arm: Semaglutide
|
Drug: Semaglutide
Semaglutide will be administered subcutaneously weekly into the abdomen, thigh or upper arm, and will be initiated at study entry at a dose of 0.25 mg once weekly, increased at week 2 to 0.5 mg once weekly, and finally increased to 1.0 mg once weekly at week 4 for continuation through week 24.
|
Outcome Measures
Primary Outcome Measures
- Change (absolute) in intra-hepatic triglyceride (IHTG) (%) [From pre-entry to week 24]
To evaluate whether 24 weeks of semaglutide will improve IHTG in ART-treated, adults with HIV, hepatic steatosis, central obesity, and insulin resistance or pre-diabetes. The primary comparison will examine the absolute change in IHTG from pre-entry to week 24.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Two separate reports of HIV-1 RNA measurements <50 copies/mL, and no HIV-1 RNA measurement >500 copies/mL, during the 48 weeks prior to entry.
-
No change in ART in 24 weeks prior to entry or plans to change during study.
-
Not meeting criteria for diabetes but with central adiposity (i.e., minimum waist circumference of ≥95 cm for individuals assigned male sex at birth or ≥94 cm for individuals assigned female sex at birth), ≥5% IHTG content, plus at least one of the following indicators of insulin resistance or pre-diabetes: fasting plasma glucose 100-125 mg/dL, HbA1c between 5.7% and <6.5%, or HOMA-IR >3.0.
-
Documented evidence of immunity to hepatitis A virus (HAV) or documented history of HAV vaccination within 30 days prior to entry.
-
CD4+ T-cell count ≥200 cells/mm3 within 30 days prior to pre-entry.
-
The following laboratory values obtained within 30 days prior to pre-entry:
-
Absolute neutrophil count (ANC) >750 cells/mm3.
-
Hemoglobin >10 g/dL for individuals assigned male sex at birth and >9 g/dL for individuals assigned female sex at birth.
-
Creatinine clearance (CrCl) ≥50 mL/min, as calculated by the CKD-Epi equation.
-
Aspartate aminotransferase (AST) (SGOT) ≤3 x ULN on at least two measures.
-
Alanine aminotransferase (ALT) (SGPT) ≤3 x ULN on at least two measures.
-
Fasting triglyceride level ≤500 mg/dL.
-
For individuals prescribed daily medications with anti-inflammatory properties, the doses must be stable.
-
For individuals taking daily lipid-lowering medications, the doses must be stable.
-
Agree to use contraception if able to become pregnant.
-
For individuals taking vitamin E (any dose), the dose must be stable.
Exclusion Criteria:
-
Pregnant, breastfeeding, or plans to become pregnant.
-
Known active hepatitis C virus (HCV) infection.
-
Active/chronic hepatitis B virus (HBV).
-
Known retinopathy (excluding remote history of cotton wool spots).
-
Known active severe delayed gastric emptying.
-
Gain or loss of >5% body weight within 12 weeks prior to study entry.
-
Any plans to change diet or exercise regimen significantly, except for the adoption of study-provided suggestions for diet and exercise, within the study period.
-
Known acute or chronic liver disease with cirrhosis or portal hypertension.
-
History of liver transplant.
-
Current diagnosis of diabetes mellitus or current use of diabetes medications, or a laboratory measurement of hemoglobin A1c ≥6.5% at screening.
-
Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN2).
-
History of unexplained hypercalcemia corrected for albumin that is >10.5 mg/dL.
-
Use of any immunomodulatory (including prednisone equivalent of ≥10 mg), HIV vaccine, investigational therapy, or TNF-α therapy within 3 months prior to study entry.
-
Use of human growth hormone, tesamorelin, supraphysiologic testosterone to achieve therapeutic blood levels, or any use of other anabolic steroids within 3 months prior to study entry or plans to start these while on study.
-
Use of estrogens or progesterones at supraphysiologic doses within 3 months prior to study entry.
-
Known allergy/sensitivity or any hypersensitivity to components of study drug or its formulation.
-
Current serious illness requiring systemic treatment and/or hospitalization.
-
Use of GLP-1 agonists within 24 weeks prior to study entry.
-
Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
-
Excessive consumption of alcohol of ≥3 months within 90 days prior to screening.
-
Known chronic pancreatitis or more than one episode of pancreatitis ever in the past.
-
Intent to use any medication likely to cause significant changes in weight during the study period.
-
Use of stavudine within 12 months prior to study entry.
-
Prior bariatric surgery (e.g., lap band, gastric sleeve, or Roux-en-Y bypass surgery) or major gastric surgery or plans to undergo weight reduction surgery while on study.
-
Individuals with any metal, implantable devices (e.g., pacemakers, prosthetics), or shrapnel, per standard MRI exclusion criteria.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 31788 Alabama CRS | Birmingham | Alabama | United States | 35294 |
| 2 | 6101 University of Colorado Hospital CRS | Aurora | Colorado | United States | 80045 |
| 3 | 201 Johns Hopkins University CRS | Baltimore | Maryland | United States | 21205 |
| 4 | 101 Massachusetts General Hospital (MGH) CRS | Boston | Massachusetts | United States | 02114 |
| 5 | 2401 Cincinnati CRS | Cincinnati | Ohio | United States | 45267-0405 |
| 6 | 31473 Houston AIDS Research Team (HART) CRS | Houston | Texas | United States | 77030 |
| 7 | 1401 University of Washington AIDS CRS | Seattle | Washington | United States | 98104 |
| 8 | 12101 Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS | Rio de Janeiro | Brazil | 21040 |
Sponsors and Collaborators
- AIDS Clinical Trials Group
- National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
- Study Chair: Kristine Erlandson, MD, MS, University of Colorado Hospital CRS
- Study Chair: Jordan E Lake, MD, MSc, Houston AIDS Research Team CRS
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ACTG A5371
- UM1AI068636