LIROH - Liraglutide for Obesity in HIV

NCT06438146 | Recruiting Phase 4

• 2 other identifiers: 2023P002985K23DK125162
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this single-arm, open label pilot study is to evaluate liraglutide at the recommended dosage administered subcutaneously + lifestyle counselling for the management of people living with HIV (PLWH) with obesity defined by a BMI ≥30 kg/m2 who are on dolutegravir-based ART. Following individual informed consent, all participants will undergo a series of basic cardiometabolic labs. They will then be initiated on liraglutide 0.6 mg administered subcutaneously, and this dose will be gradually increased over a period of 4 weeks to a dose of 3.0 mg daily. Alongside drug administration, participants will receive lifestyle counselling regarding diet and physical activity. Following completion of a 12-week "on treatment" period, liraglutide will be stopped and participants will be followed for an additional 12-weeks off treatment. Body weight, cardiometabolic risk parameters, and a suite of patient-reported outcomes regarding diet, physical activity, sleep, and quality of life will be assessed periodically over the course of the study.

Conditions

Obesity; HIV Infections

Keywords

HIV; Obesity; Liraglutide; Behavior; Exercise; Lifestyle counseling

Outcome Measures

Primary Outcomes (6)

• Proportion of participants who screen and enroll among those approached

  This will be expressed in terms of the proportion of participants who attend screening and enrolment visits among the total number who are approached regarding interest in study participation.

  Measured at screening

• Time to reach study enrollment target

  Measured at enrollment

• Study retention rate at 12 weeks

  This will be expressed as a proportion of participants who remain in the study after the 12 week "on treatment" period among those enrolled.

  Measured at Visit 4 at 12 weeks

• Study retention rate at 24 weeks

  This will be expressed as a proportion of participants who remain in the study after the full 24 weeks of study procedures are completed among those enrolled.

  Measured at End of Study at 24 weeks

• Rate of adherence to treatment over 12 weeks

  The investigators will assess volume remaining in the injector pens and provide a percentage of doses per participant that remained unused at the end of the 12-week period on treatment.

  Measured at Visit 4 at 12 weeks

• Embedded qualitative interviews regarding the acceptability of liraglutide for obesity management

  This will be open-ended responses to a brief exit interview about acceptability and feasibility.

  Measured at End of Study at 24 weeks

Secondary Outcomes (14)

• Incidence of treatment-emergent adverse events as defined in this protocol

  From the initiation of treatment until the date of a treatment-emergent adverse event, assessed up to 24 weeks.

• Incidence of serious adverse events (SAEs), as defined in this protocol

  From the initiation of treatment until the date of a serious adverse event, assessed up to 24 weeks.

• Change in body weight following 12 weeks on treatment

  Measured at Visit 4 at 12 weeks

• Change in body weight over 24 weeks (12 weeks on + 12 weeks off treatment)

  Measured at End of Study at 24 weeks

• Change in HbA1c following 12 weeks on treatment

  Measured at Visit 4 at 12 weeks

Other Outcomes (10)

• Change in blood pressure following 12 weeks on treatment

  Measured at Visit 4 at 12 weeks

• Change in blood pressure over 24 weeks (12 weeks on + 12 weeks off treatment)

  Measured at End of Study at 24 weeks

• Change in lipids following 12 weeks on treatment

  Measured at Visit 4 at 12 weeks

Study Arms (1)

Lirgalutide

EXPERIMENTAL

Following individual informed consent, all participants will undergo a series of basic cardiometabolic labs. They will then be initiated on liraglutide 0.6 mg administered subcutaneously, and this dose will be gradually increased over a period of 4 weeks to a dose of 3.0mg daily. Alongside drug administration, participants will receive lifestyle counselling regarding diet and physical activity. Following completion of a 12-week "on treatment" period, liraglutide will be stopped and participants will be followed for an additional 12-weeks off treatment. Body weight, cardiometabolic risk parameters, and a suite of patient-reported outcomes regarding diet, physical activity, sleep, and quality of life will be assessed periodically over the course of the study.

Drug: Liraglutide

Interventions

Liraglutide DRUG

Dosing regimen: In this study protocol, liraglutide dosing will be implemented as follows: Liraglutide will be started at a dose of 0.6 mg per day. Participants will be taught to use the injection pen and will be observed giving the first injection. The dose will then be increased by 0.6 mg each week to a maximum dosage of 3.0 mg per day at the end of 4 weeks. This corresponds to the following dosing schedule: Week 1: 0.6 mg per day for one week Week 2: 1.2 mg per day for one week Week 3: 1.8 mg per day for one week Week 4: 2.4 mg per day for one week Week 5-12: 3.0 mg per day for 8 weeks Week 13-24: No drug administration

Also known as: Saxenda

Lirgalutide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to give written informed consent to participate in the study
• Able to comply with all study procedures, including daily subcutaneous injections
• Adults ≥18 years old
• PLWH on dolutegravir-based ART for ≥6 months
• Documented HIV-1 viral load in the past 6 months confirming the participant is virologically suppressed
• BMI ≥30 kg/m2
• Desiring weight loss
• Willing to undertake lifestyle change
• Not on any weight loss agent for the duration of the study

You may not qualify if:

• Self-reported history of diabetes
• Current use of medications for diabetes
• Known contraindications to liraglutide, such as hypersensitivity to a component of the drug
• Current pregnancy or desire to become pregnant
• History of pancreatitis
• History of thyroid disease
• History of harmful use of alcohol
• Clinically unstable in the opinion of the investigator

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Africa Health Research Institute Clinical Trials Unit

Mtubatuba, 3935, South Africa

RECRUITING

Related Publications (10)

• Venter WDF, Moorhouse M, Sokhela S, Fairlie L, Mashabane N, Masenya M, Serenata C, Akpomiemie G, Qavi A, Chandiwana N, Norris S, Chersich M, Clayden P, Abrams E, Arulappan N, Vos A, McCann K, Simmons B, Hill A. Dolutegravir plus Two Different Prodrugs of Tenofovir to Treat HIV. N Engl J Med. 2019 Aug 29;381(9):803-815. doi: 10.1056/NEJMoa1902824. Epub 2019 Jul 24.

  PMID: 31339677 BACKGROUND

• Venter WDF, Sokhela S, Simmons B, Moorhouse M, Fairlie L, Mashabane N, Serenata C, Akpomiemie G, Masenya M, Qavi A, Chandiwana N, McCann K, Norris S, Chersich M, Maartens G, Lalla-Edward S, Vos A, Clayden P, Abrams E, Arulappan N, Hill A. Dolutegravir with emtricitabine and tenofovir alafenamide or tenofovir disoproxil fumarate versus efavirenz, emtricitabine, and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection (ADVANCE): week 96 results from a randomised, phase 3, non-inferiority trial. Lancet HIV. 2020 Oct;7(10):e666-e676. doi: 10.1016/S2352-3018(20)30241-1.

  PMID: 33010240 BACKGROUND

• Manne-Goehler J, Rahim N, van Empel E, de Vlieg R, Chamberlin G, Ihama A, Castle A, Mabweazara S, Venter WDF, Chandiwana N, Levitt NS, Siedner M. Perceptions of Health, Body Size, and Nutritional Risk Factors for Obesity in People with HIV in South Africa. AIDS Behav. 2024 Jan;28(1):367-375. doi: 10.1007/s10461-023-04152-7. Epub 2023 Aug 26.

  PMID: 37632604 BACKGROUND

• Chandiwana NC, Siedner MJ, Marconi VC, Hill A, Ali MK, Batterham RL, Venter WDF. Weight Gain After HIV Therapy Initiation: Pathophysiology and Implications. J Clin Endocrinol Metab. 2024 Jan 18;109(2):e478-e487. doi: 10.1210/clinem/dgad411.

  PMID: 37437159 BACKGROUND

• Magodoro IM, Olivier S, Gareta D, Koole O, Modise TH, Gunda R, Herbst K, Pillay D, Wong EB, Siedner MJ. Linkage to HIV care and hypertension and diabetes control in rural South Africa: Results from the population-based Vukuzazi Study. PLOS Glob Public Health. 2022 Nov 2;2(11):e0001221. doi: 10.1371/journal.pgph.0001221. eCollection 2022.

  PMID: 36962629 BACKGROUND

• Rubino DM, Greenway FL, Khalid U, O'Neil PM, Rosenstock J, Sorrig R, Wadden TA, Wizert A, Garvey WT; STEP 8 Investigators. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial. JAMA. 2022 Jan 11;327(2):138-150. doi: 10.1001/jama.2021.23619.

  PMID: 35015037 BACKGROUND

• Wadden TA, Bailey TS, Billings LK, Davies M, Frias JP, Koroleva A, Lingvay I, O'Neil PM, Rubino DM, Skovgaard D, Wallenstein SOR, Garvey WT; STEP 3 Investigators. Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial. JAMA. 2021 Apr 13;325(14):1403-1413. doi: 10.1001/jama.2021.1831.

  PMID: 33625476 BACKGROUND

• Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar 18;384(11):989-1002. doi: 10.1056/NEJMoa2032183. Epub 2021 Feb 10.

  PMID: 33567185 BACKGROUND

• Hyle EP, Bekker LG, Martey EB, Huang M, Xu A, Parker RA, Walensky RP, Middelkoop K. Cardiovascular risk factors among ART-experienced people with HIV in South Africa. J Int AIDS Soc. 2019 Apr;22(4):e25274. doi: 10.1002/jia2.25274.

  PMID: 30990252 BACKGROUND

• Bailin SS, Gabriel CL, Wanjalla CN, Koethe JR. Obesity and Weight Gain in Persons with HIV. Curr HIV/AIDS Rep. 2020 Apr;17(2):138-150. doi: 10.1007/s11904-020-00483-5.

  PMID: 32072466 BACKGROUND

MeSH Terms

Conditions

Obesity; HIV Infections; Behavior; Motor Activity

Interventions

Liraglutide

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Jennifer Manne-Goehler, MD, ScD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer Manne-Goehler, MD, ScD

CONTACT

7542246060; jmanne@bwh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: May 2, 2024
• First Posted: May 31, 2024
• Study Start: May 2, 2024
• Primary Completion: May 1, 2025
• Study Completion: May 1, 2025
• Last Updated: May 31, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: The IPD data will be shared in accordance with AHRI Data Access Policy and Data Management Plan within two years of completion.
• Access Criteria: Access to the IPD and the associated documents will require completion of the online data access application form accessible on the AHRI Data repository. AHRI bona fide data users are required to abide by the data use conditions stipulated on the application for access to the data.

Locations

ZA (1)