Incretin Microdosing for Cardiometabolic Health in People With HIV

NCT ID: NCT07325500

Last Updated: 2026-01-08

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-02-01
• Study Completion Date: 2029-06-30

Brief Summary

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.

Conditions

Weight Gain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

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

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Dose escalation to 2 mg semaglutide weekly then no semaglutide

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

University of Colorado Denver - Anschutz Medical Campus (UCD-AMC)

UNKNOWN

Sponsor Role: collaborator

Massachusetts General Hospital (MGH)

UNKNOWN

Sponsor Role: collaborator

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role: lead

Responsible Party

Jordan Elizabeth Lake

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jordan Lake, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center, Houston

Locations

The University of Texas Health Science Center at Houston

Houston, Texas, United States

Countries

United States

Central Contacts

Jordan E Lake, MD, MSc

Role: CONTACT

Jordan.E.Lake@uth.tmc.edu

713-500-6767

Arezou S Akha

Role: CONTACT

arezou.sadighiakha@uth.tmc.edu

713-500-5541

Facility Contacts

Jordan E Lake, MD, MSc

Role: primary

Jordan.E.Lake@uth.tmc.edu

713-500-6767

Arezou S Akha

Role: backup

arezou.sadighiakha@uth.tmc.edu

713-500-5541

Other Identifiers

1R01DK142171-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HSC-MS-25-0376

Identifier Type: -

Identifier Source: org_study_id