Incretin Microdosing for Cardiometabolic Health in People With HIV

Official title

Incretin Microdosing for Cardiometabolic Health in People With HIV: The REINFORCE Trial

Overview

The objectives of this study are as follows: Primary Objective * To determine the rate of weight regain in people living with human immunodeficiency virus (HIV) (PWH) receiving semaglutide microdosing vs. no additional drug following induction therapy. Secondary Objectives * To evaluate the tolerability of semaglutide microdosing in adults with HIV. * To evaluate changes in weight, waist circumference (WC) and body mass index (BMI) over 12 weeks (W) of semaglutide weight loss induction and 48 W of semaglutide microdosing therapy.

Interventions

• Drug Dose escalation to 2 mg semaglutide weekly then semaglutide microdosing at 0.5 mg weekly
  Participants will initiate semaglutide at 0.25 milligrams (mg) subcutaneously per week with dose titration up to 2.0 mg subcutaneously per week, over a total of 12 weeks. Dose titration will occur as follows: 0.25 mg weekly for 2 weeks, then 0.5 mg weekly for 2 weeks, then 1 mg weekly for 4 weeks, then 2.0 mg weekly for 4 weeks. Then, participants in this arm will receive microdosing with semaglutide at 0.5 mg subcutaneously every week during weeks 13-60.
• Drug Dose escalation to 2 mg semaglutide weekly then no semaglutide
  Participants will initiate semaglutide at 0.25 milligrams (mg) subcutaneously per week with dose titration up to 2.0 mg subcutaneously per week, over a total of 12 weeks. Dose titration will occur as follows: 0.25 mg weekly for 2 weeks, then 0.5 mg weekly for 2 weeks, then 1 mg weekly for 4 weeks, then 2.0 mg weekly for 4 weeks. Then, participants in this arm will receive no semaglutide during weeks 13-60.

Primary outcome measures

• Percent weight regain from weeks 12-60 (microdosing period) [Time frame: from week 12 to week 60]

Secondary outcome measures (7)

• Tolerability of semaglutide microdosing in participants as indicated by total number of serious adverse events (SAEs) and adverse events (AEs) [Time frame: From baseline through week 60]
• Absolute change in weight [Time frame: Baseline, 12 weeks, 60 weeks]
• Percent change in weight [Time frame: Baseline, 12 weeks, 60 weeks]
• Absolute change in body mass index (BMI) [Time frame: Baseline, 12 weeks, 60 weeks]
• Percent change in body mass index (BMI) [Time frame: Baseline, 12 weeks, 60 weeks]
• Absolute change in minimum waist circumference [Time frame: Baseline, 12 weeks, 60 weeks]
• Percent change in minimum waist circumference [Time frame: Baseline, 12 weeks, 60 weeks]

Eligibility criteria

Inclusion criteria

• Confirmed human immunodeficiency virus type 1 (HIV-1)
• On antiretroviral therapy (ART) for greater than or equal to 24 weeks prior to entry and no change in regimen in the 12 weeks prior to entry or planned change for the study duration
• HIV-1 ribonucleic acid (RNA) <200 copies/mL at screening
• BMI greater than or equal to 30 kg/m2 or greater than or equal to 27 kg/m2 if also with greater than or equal to 1 weight-related comorbidity
• If taking anti-inflammatory or blood-pressure-/lipid-/glucose-lowering medications, no change in dose for greater than or equal to 12 weeks prior to entry and no plans to dose escalate for the study duration
• All participants must be willing and able to provide written informed consent and undergo all required study procedures

Exclusion criteria

• Weight greater than or equal to 400 pounds \[due to dual X-ray absorptiometry (DXA) machine limitations\] or unexplained weight change greater than or equal to 5% in the 12 weeks prior to entry
• Diagnosis of or on treatment for diabetes mellitus (stable metformin dosing for pre-diabetes not excluded)
• Current or planned use of medications for the treatment of obesity, or medications likely to cause significant changes in weight, during the study period
• Plans to newly engage in formal, intensive physical activity or diet (such as ketogenic or very low carbohydrate) programs during the study period
• Active eating disorder
• Use of human growth hormone, tesamorelin or anabolic steroids <12 weeks prior to entry, unless on a stable dose for >24 weeks prior to entry, or plans to start any of these medications while on study
• Active, severe delayed gastric emptying
• Prior bariatric surgery or major gastric surgery or plans for weight reduction surgery while on study
• Known retinopathy
• Personal or first-degree relative history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2
• Untreated, poorly controlled or previously undiagnosed thyroid disease
• Chronic pancreatitis
• Known allergy/sensitivity to Glucagon-Like Peptide-1 Receptor Agonist (GLP-1RA)
• Poorly controlled or previously undiagnosed thyroid disease, defined as thyroid-stimulating hormone (TSH) <0.5 or >10 milli-international units per liter (mIU/L) at screening
• Active drug or alcohol use that, in the opinion of the investigator, would interfere with adherence to study requirements
• Pregnancy, nursing or plans for either during the study period
• Use of planned use of any immunomodulatory therapy HIV vaccine, investigational therapy or tumor necrosis factor (TNF-α) therapy during the study period
• Current serious illness requiring systemic treatment and/or hospitalization, in the opinion of site investigator

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• The University of Texas Health Science Center at Houston — Houston

Identifiers

NCT: NCT07325500 · HSC-MS-25-0376 · 1R01DK142171-01A1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗