The SLIM LIVER Study

• Status: Active, not recruiting
• Trial end date: 2023-08-30
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: AIDS Clinical Trials Group
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID)

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:

1. Absolute neutrophil count (ANC) >750 cells/mm3.

2. Hemoglobin >10 g/dL for individuals assigned male sex at birth and >9 g/dL for individuals assigned female sex at birth.

3. Creatinine clearance (CrCl) ≥50 mL/min, as calculated by the CKD-Epi equation.

4. Aspartate aminotransferase (AST) (SGOT) ≤3 x ULN on at least two measures.

5. Alanine aminotransferase (ALT) (SGPT) ≤3 x ULN on at least two measures.

6. 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.