The SLIM LIVER Study (SLIM LIVER)

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Insulin Resistance; Adiposity; Hepatic Steatosis; HIV-1-infection; Pre-diabetes
• Intervention / Treatment: Drug: Semaglutide

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro, Brazil, 21040
    • 12101 Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • 31788 Alabama CRS
  • Colorado
    • Aurora, Colorado, United States, 80045
      • 6101 University of Colorado Hospital CRS
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • 201 Johns Hopkins University CRS
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • 101 Massachusetts General Hospital (MGH) CRS
  • Ohio
    • Cincinnati, Ohio, United States, 45267-0405
      • 2401 Cincinnati CRS
  • Texas
    • Houston, Texas, United States, 77030
      • 31473 Houston AIDS Research Team (HART) CRS
  • Washington
    • Seattle, Washington, United States, 98104
      • 1401 University of Washington AIDS CRS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: AIDS Clinical Trials Group
• Collaborators: 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 record dates

Study Major Dates

• Study Start (Actual): October 1, 2021
• Primary Completion (Anticipated): August 30, 2023
• Study Completion (Anticipated): August 30, 2023

Study Registration Dates

• First Submitted: December 7, 2022
• First Submitted That Met QC Criteria: December 7, 2022
• First Posted (Actual): December 16, 2022

Study Record Updates

• Last Update Posted (Actual): December 16, 2022
• Last Update Submitted That Met QC Criteria: December 7, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Liver Diseases; Hyperinsulinism; Fatty Liver; Prediabetic State; Insulin Resistance
• Other Study ID Numbers: ACTG A5371; UM1AI068636 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Individual participant data that underlie results in the publication, after deidentification.
• IPD Sharing Time Frame: Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH.

IPD Sharing Access Criteria

• With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group.
• For what types of analyses? To achieve aims in the proposal approved by the AIDS Clinical Trials Group.
• By what mechanism will data be made available?

Researchers may submit a request for access to data using the AIDS Clinical Trials Group "Data Request" form at:

https://actgnetwork.org/about-actg/templates-and-forms. Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data."

• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No