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ObesityPhase 4LIROHNCT06438146

LIROH - Liraglutide for Obesity in HIV

A Phase 4 study testing Liraglutide in people with Obesity and HIV Infections, run by Brigham and Women's Hospital at 1 site in South Africa.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Obesity, HIV Infections
What is being tested?
Liraglutide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteSouth Africa
Study dates
2 May 2024to May 2025
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 9Show fewer
  • Desiring weight loss
  • Willing to undertake lifestyle change
  • Not on any weight loss agent for the duration of the study

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

Jennifer Manne-Goehler, MD, ScD contact

7542246060

jmanne@bwh.harvard.edu

South Africa1 site, 1 recruiting

  • Africa Health Research Institute Clinical Trials Unit

    Mtubatuba, 3935

    Ngundu Behuhuma, MBChB, 082 964 0652, ngundu.behuhuma@ahri.org

    Ngundu Behuhuma, MBChB

    Recruiting

Other trials in South Africa

About this study

Official title: Liraglutide for Management of Obesity in People Living With HIV on Dolutegravir-based Antiretroviral Therapy: a Single-arm Acceptability Study in South Africa

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.

Read the detailed description

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.

Being tested
Liraglutide
Keywords
HIV, Obesity, Liraglutide, Behavior, Exercise, Lifestyle counseling
Medical subject headings
Obesity, HIV Infections, Behavior, Motor Activity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LiraglutideDrug

    Also called Saxenda

    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

Study groups in NCT06438146
Study groupRoleWhat they receive
LirgalutideExperimentalFollowing 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.
Receives: Drug: Liraglutide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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: Measured at screening

  2. Time to reach study enrollment target

    Measured: Measured at enrollment

  3. 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: Measured at Visit 4 at 12 weeks

  4. 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: Measured at End of Study at 24 weeks

  5. 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: Measured at Visit 4 at 12 weeks

  6. 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: Measured at End of Study at 24 weeks

Secondary outcomes (14)

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

    The investigators will report incidence of TEAEs up to 24 weeks (12 weeks on + 12 weeks off treatment)

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

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

    The investigators will report incidence of SAEs up to 24 weeks (12 weeks on + 12 weeks off treatment)

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

  3. Change in body weight following 12 weeks on treatment

    Body weight will be measured in the study at both enrolment and after 12 weeks on treatment (Visit 4); these will be used to calculate a continuous change in kg.

    Measured: Measured at Visit 4 at 12 weeks

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

    Body weight will be measured in the study at both enrolment and after 24 weeks on treatment (EOS); these will be used to calculate a continuous change in kg.

    Measured: Measured at End of Study at 24 weeks

  5. Change in HbA1c following 12 weeks on treatment

    HbA1c will be measured at enrolment and at Visit 4; here investigators will calculate the difference between these measures (in %).

    Measured: Measured at Visit 4 at 12 weeks

  6. Change in HbA1c over 24 weeks (12 weeks on + 12 weeks off treatment)

    HbA1c will be measured at enrolment and at EOS; here investigators will calculate the difference between these measures (in %).

    Measured: Measured at End of Study at 24 weeks

  7. Change in fasting plasma glucose following 12 weeks on treatment

    Fasting glucose will be measured at enrolment and at Visit 4; investigators will calculate the difference between these measures (in mmol/L).

    Measured: Measured at Visit 4 at 12 weeks

  8. Change in fasting plasma glucose over 24 weeks (12 weeks on + 12 weeks off treatment)

    Fasting glucose will be measured at enrolment and at EOS; investigators will calculate the difference between these measures (in mmol/L).

    Measured: Measured at End of Study at 24 weeks

  9. Change in depressive symptoms following 12 weeks on treatment

    This will be defined as the difference in depression score per the Patient Health Questionnaire (PHQ-9) at enrolment and Visit 4. The minimum value is 1 and the maximum is 27, where the greater the total score, the greater severity of depression.

    Measured: Measured at Visit 4 at 12 weeks

  10. Change in depressive symptoms over 24 weeks (12 weeks on + 12 weeks off treatment)

    This will be defined as the difference in depression score per the Patient Health Questionnaire (PHQ-9) at enrolment and EOS. The minimum value is 1 and the maximum is 27, where the greater the total score, the greater severity of depression.

    Measured: Measured at End of Study at 24 weeks

  11. Change in physical activity level following 12 weeks on treatment

    This will be defined as the difference in physical activity expressed in MET-minutes per week, where MET minutes represent the amount of energy expended carrying out physical activity, per the International Physical Activity Questionnaire (IPAQ) at enrolment and Visit 4.

    Measured: Measured at Visit 4 at 12 weeks

  12. Change in physical activity level over 24 weeks (12 weeks on + 12 weeks off treatment)

    This will be defined as the difference in physical activity expressed in MET-minutes, where MET minutes represent the amount of energy expended carrying out physical activity, per week per the International Physical Activity Questionnaire (IPAQ) at enrolment and EOS.

    Measured: Measured at End of Study at 24 weeks

  13. Change in dietary habits following 12 weeks on treatment

    This will be defined as the difference in total servings of fruits and vegetables, change in frequency of sugar-sweetened beverage intake, and change frequency of fast food intake from enrolment to Visit 4.

    Measured: Measured at Visit 4 at 12 weeks

  14. Change in dietary habits over 24 weeks (12 weeks on + 12 weeks off treatment)

    This will be defined as the difference in total servings of fruits and vegetables, change in frequency of sugar-sweetened beverage intake, and change frequency of fast food intake from enrolment to EOS.

    Measured: Measured at End of Study at 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 May 2024
  2. Study start2 May 2024
  3. Primary completionMay 2025 (estimated)
  4. Study completionMay 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06438146
Sponsor's protocol ID
2023P002985
Other IDs
K23DK125162
Acronym
LIROH
Status last verified
May 2024
First submitted
2 May 2024
Last updated
31 May 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Anonymized data as allowable

Publications

  • 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.

    PubMed 31339677

  • 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.

    PubMed 33010240

  • 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.

    PubMed 37632604

  • 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.

    PubMed 37437159

  • 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.

    PubMed 36962629

  • 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.

    PubMed 35015037

  • 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.

    PubMed 33625476

  • 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.

    PubMed 33567185

  • 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.

    PubMed 30990252

  • 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.

    PubMed 32072466

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Liraglutide in people with Obesity and HIV Infections, run by Brigham and Women's Hospital at 1 site in South Africa.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 31 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Jennifer Manne-Goehler, MD, ScD (7542246060, jmanne@bwh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of participants who screen and enroll among those approached (time frame: Measured at screening). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06438146, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 May 2024.

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