LIROH - Liraglutide for Obesity in HIV

NCT ID: NCT06438146

Last Updated: 2024-05-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-05-02

Study Completion Date

2025-05-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

South Africa has the largest population of PLWH globally, with a prevalence of 17% in adults or 7.2 million PLWH. The rapid scale-up of ART programs has resulted in \>6 million PLWH on treatment, significant gains in life expectancy, and a large population of aging PLWH. With increasing life expectancy, obesity and type 2 diabetes have become growing threats for PLWH in South Africa and globally. One recent study found that 63% of PLWH are overweight or obese, and 6% have diabetes in this setting.

This elevated risk of obesity in PLWH in South Africa is likely due to a confluence of both general considerations and HIV-specific factors. First, South Africa has experienced an accelerated background epidemic of metabolic disease in the general population with a prevalence of overweight and obesity that is nearly equal to that of high-income countries. Additionally, the International Diabetes Federation estimates that approximately 15.5 million adults are living with diabetes in the African Region, and projects it to grow to 41 million by 2045. As part of this background epidemic of metabolic disease, South Africa is also experiencing a nutrition transition, with widespread availability of processed and refined foods as well as sugar-sweetened beverages.

Regarding HIV-specific issues, in 2019 the first-line ART regimen for the South African national HIV treatment program transitioned to TLD. TLD is generally very safe and well-tolerated and has a high barrier to HIV resistance but this transition to this regimen has been associated with risk of excess weight gain at the population level. Both clinical trials and observational studies conducted in South Africa have shown substantial increases in body weight in those who are initiating this ART regimen newly and among those who are suppressed and switched, especially women. Given this, there is a growing risk of obesity in PLWH in this context and a need for management strategies to address this increasingly prevalent comorbidity.

Preventing the metabolic complications of HIV in South Africa and worldwide requires urgent solutions. To date, obesity management and diabetes prevention have largely consisted of behavioural interventions such as the Diabetes Prevention Program and related lifestyle modification efforts, focused on improving diet and increasing physical activity. However, in the past several years, novel anti-obesity pharmacologic agents such as the glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown enormous promise for obesity management and diabetes prevention in people who are HIV-negative (8-10). However, this drug class has a very limited evidence base in PLWH and relatively scant data from sub-Saharan African populations.

Currently, liraglutide is the only GLP-1 RA approved for obesity management in South Africa and this protocol proposes to use the drug for its labelled indication of "weight loss in addition to diet and exercise in adults aged 18 and above who have: (1) a BMI of 30 or greater (obese) or (2) a BMI of greater than 27 and less than 30 (overweight) and weight related health problems (such as diabetes, high blood pressure, hypercholesterolemia, or obstructive sleep apnoea).

This evidence gap motivates further inquiry into GLP-1 RAs such as liraglutide as one potential approach to obesity management and prevention of diabetes in PLWH who have comorbid obesity in South Africa, with implications for PLWH in other contexts. In this proposal, the investigators seek to further this important area of inquiry by evaluating the acceptability of liraglutide along with lifestyle counselling in PLWH who have obesity and are stable on dolutegravir-based ART in South Africa.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Obesity HIV Infections

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

HIV Obesity Liraglutide Behavior Exercise Lifestyle counseling

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Lirgalutide

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.

Group Type EXPERIMENTAL

Liraglutide

Intervention Type 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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Liraglutide

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

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Saxenda

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

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

Exclusion Criteria

1. Self-reported history of diabetes
2. Current use of medications for diabetes
3. Known contraindications to liraglutide, such as hypersensitivity to a component of the drug
4. Current pregnancy or desire to become pregnant
5. History of pancreatitis
6. History of thyroid disease
7. History of harmful use of alcohol
8. Clinically unstable in the opinion of the investigator
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

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

NIH

Sponsor Role collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Jennifer M. Manne-Goehler, MD, SCD

Assistant Professor of Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Jennifer Manne-Goehler, MD, ScD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Africa Health Research Institute Clinical Trials Unit

Mtubatuba, , South Africa

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

South Africa

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Jennifer Manne-Goehler, MD, ScD

Role: CONTACT

Phone: 7542246060

Email: [email protected]

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Ngundu Behuhuma, MBChB

Role: primary

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 31339677 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33010240 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 37632604 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 37437159 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 36962629 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 35015037 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33625476 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33567185 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30990252 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32072466 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

K23DK125162

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2023P002985

Identifier Type: -

Identifier Source: org_study_id