Incretin Microdosing for Cardiometabolic Health in People With HIV (REINFORCE)

The University of Texas System (UT)

Status and phase: Not yet enrolling; Phase 2

Conditions: Weight Gain

Treatments: Drug: Dose escalation to 2 mg semaglutide weekly then no semaglutide; Drug: Dose escalation to 2 mg semaglutide weekly then semaglutide microdosing at 0.5 mg weekly

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT07325500

HSC-MS-25-0376

1R01DK142171-01A1 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Enrollment: 30 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

30 participants in 2 patient groups

Dose escalation to 2 mg semaglutide weekly then semaglutide microdosing at 0.5 mg weekly

Experimental group

Description:

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.

Treatment:

Drug: Dose escalation to 2 mg semaglutide weekly then semaglutide microdosing at 0.5 mg weekly

Dose escalation to 2 mg semaglutide weekly then no semaglutide

Experimental group

Description:

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.

Treatment:

Drug: Dose escalation to 2 mg semaglutide weekly then no semaglutide