Clinical trial NCT06438146: LIROH - Liraglutide for Obesity in HIV
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Obesity
HIV Infections
Keywords: HIV
Obesity
Liraglutide
Behavior
Exercise
Lifestyle counseling
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2024-05-31
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of participants who screen and enroll among those approached
timeFrame: Measured at screening
measure: Time to reach study enrollment target
timeFrame: Measured at enrollment
measure: Study retention rate at 12 weeks
timeFrame: Measured at Visit 4 at 12 weeks
measure: Study retention rate at 24 weeks
timeFrame: Measured at End of Study at 24 weeks
measure: Rate of adherence to treatment over 12 weeks
timeFrame: Measured at Visit 4 at 12 weeks
measure: Embedded qualitative interviews regarding the acceptability of liraglutide for obesity management
timeFrame: Measured at End of Study at 24 weeks
Secondary outcomes:
measure: Incidence of treatment-emergent adverse events as defined in this protocol
timeFrame: From the initiation of treatment until the date of a treatment-emergent adverse event, assessed up to 24 weeks.
measure: Incidence of serious adverse events (SAEs), as defined in this protocol
timeFrame: From the initiation of treatment until the date of a serious adverse event, assessed up to 24 weeks.
measure: Change in body weight following 12 weeks on treatment
timeFrame: Measured at Visit 4 at 12 weeks
measure: Change in body weight over 24 weeks (12 weeks on + 12 weeks off treatment)
timeFrame: Measured at End of Study at 24 weeks
measure: Change in HbA1c following 12 weeks on treatment
timeFrame: Measured at Visit 4 at 12 weeks
measure: Change in HbA1c over 24 weeks (12 weeks on + 12 weeks off treatment)
timeFrame: Measured at End of Study at 24 weeks
measure: Change in fasting plasma glucose following 12 weeks on treatment
timeFrame: Measured at Visit 4 at 12 weeks
measure: Change in fasting plasma glucose over 24 weeks (12 weeks on + 12 weeks off treatment)
timeFrame: Measured at End of Study at 24 weeks
measure: Change in depressive symptoms following 12 weeks on treatment
timeFrame: Measured at Visit 4 at 12 weeks
measure: Change in depressive symptoms over 24 weeks (12 weeks on + 12 weeks off treatment)
timeFrame: Measured at End of Study at 24 weeks
measure: Change in physical activity level following 12 weeks on treatment
timeFrame: Measured at Visit 4 at 12 weeks
measure: Change in physical activity level over 24 weeks (12 weeks on + 12 weeks off treatment)
timeFrame: Measured at End of Study at 24 weeks
measure: Change in dietary habits following 12 weeks on treatment
timeFrame: Measured at Visit 4 at 12 weeks
measure: Change in dietary habits over 24 weeks (12 weeks on + 12 weeks off treatment)
timeFrame: Measured at End of Study at 24 weeks
Other outcomes:
measure: Change in blood pressure following 12 weeks on treatment
timeFrame: Measured at Visit 4 at 12 weeks
measure: Change in blood pressure over 24 weeks (12 weeks on + 12 weeks off treatment)
timeFrame: Measured at End of Study at 24 weeks
measure: Change in lipids following 12 weeks on treatment
timeFrame: Measured at Visit 4 at 12 weeks
measure: Change in lipids over 24 weeks (12 weeks on + 12 weeks off treatment)
timeFrame: Measured at End of Study at 24 weeks
measure: Change in waist circumference following 12 weeks on treatment
timeFrame: Measured at Visit 4 at 12 weeks
measure: Change in waist circumference over 24 weeks (12 weeks on + 12 weeks off treatment)
timeFrame: Measured at End of Study at 24 weeks
measure: Change in quality of life following 12 weeks on treatment per the World Health Organization's Quality of Life Instrument in HIV Infection
timeFrame: Measured at Visit 4 at 12 weeks
measure: Change in quality of life over 24 weeks (12 weeks on + 12 weeks off treatment) per the World Health Organization's Quality of Life Instrument in HIV Infection
timeFrame: Measured at End of Study at 24 weeks
measure: Change in sleep quality following 12 weeks on treatment per the Pittsburgh Sleep Quality Index
timeFrame: Measured at Visit 4 at 12 weeks
measure: Change in sleep quality over 24 weeks (12 weeks on + 12 weeks off treatment) per the Pittsburgh Sleep Quality Index
timeFrame: Measured at End of Study at 24 weeks
Locations:
city: Mtubatuba
country: South Africa
facility: Africa Health Research Institute Clinical Trials Unit
Study officials:
affiliation: Brigham and Women's Hospital
name: Jennifer Manne-Goehler, MD, ScD
role: PRINCIPAL_INVESTIGATOR
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