The SLIM LIVER Study

Insulin Resistance Clinical Trial

— SLIM LIVER  

Official title:

A Single-Arm, Open-Label, Pilot Study of Semaglutide for Non-Alcoholic Fatty Liver Disease (NAFLD), a Metabolic Syndrome With Insulin Resistance, Increased Hepatic Lipids, and Increased Cardiovascular Disease Risk (The SLIM LIVER Study)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05654051
• Other study ID #: ACTG A5371
• Secondary ID: UM1AI068636
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 1, 2021
• Est. completion date: August 30, 2023

Study information

• Verified date: December 2022
• Source: AIDS Clinical Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 51
• Est. completion date: August 30, 2023
• Est. primary completion date: August 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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-a 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.

Related Conditions & MeSH terms

• Adiposity
• Fatty Liver
• Hepatic Steatosis
• HIV-1-infection
• Insulin Resistance
• Pre-diabetes
• Prediabetic State

Intervention

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.

Locations

Country	Name	City	State
Brazil	12101 Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS	Rio de Janeiro
United States	6101 University of Colorado Hospital CRS	Aurora	Colorado
United States	201 Johns Hopkins University CRS	Baltimore	Maryland
United States	31788 Alabama CRS	Birmingham	Alabama
United States	101 Massachusetts General Hospital (MGH) CRS	Boston	Massachusetts
United States	2401 Cincinnati CRS	Cincinnati	Ohio
United States	31473 Houston AIDS Research Team (HART) CRS	Houston	Texas
United States	1401 University of Washington AIDS CRS	Seattle	Washington

Sponsors (2)

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

Countries where clinical trial is conducted

United States,  Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change (absolute) in intra-hepatic triglyceride (IHTG) (%)	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.	From pre-entry to week 24