Clinical trial NCT04174755: Semaglutide's Efficacy in Achieving Weight Loss for Those With HIV
Official title: Semaglutide's Efficacy in Achieving Weight Loss for Those With HIV
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Obesity
HIV-1-infection
Keywords: obesity
HIV
weight loss
GLP-1 analogue
immune activation
viral reservoir
gut microbiome
Lead sponsor: University College Dublin
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
name: Rush University Medical Center
First posted: 2019-11-22
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The prevalence of obesity is rising worldwide, both in low- and high-income countries, including people with HIV (PWH). Semaglutide's efficacy in achieving weight loss in obese PWH is still unexplored. The aim of this study is to assess the efficacy and safety of semaglutide in achieving greater weight loss compared to diet and excercise alone in obese PWH and to explore the effect of semaglutide on the immune function, markers of immune activation, viral reservoir, markers of glucose and lipid metabolism and gut microbiome.

Detailed description: A randomised, controlled, parallel-group, open-label study comparing treatment with the GLP-1 analogue semaglutide in combination with lifestyle interventions to lifestyle interventions alone in obese PWH.

The study will enroll HIV-1 infected patients ≥ 18 years with BMI ≥30kg/m2 or BMI ≥27kg/m2 and hypertension, dyslipidaemia or type 2 diabetes mellitus.

Primary objective: To assess the efficacy of semaglutide as an adjunct to diet and exercise in achieving greater weight loss in obese PWH as compared to diet and exercise alone.

Secondary objectives:

* To explore the effect of semaglutide on markers of immune function and HIV viral reservoirs in obese PWH.
* To explore the effect of semaglutide on markers of glucose and lipid metabolism in obese PWH.
* To explore the effect of semaglutide on markers of inflammation and gut microbial translocation in obese PWH.
* To assess the safety of semaglutide in obese PWH on stable ART.

Eligibility criteria: Inclusion Criteria:

* Be over 18 years old
* Be HIV-1 antibody positive as determined by a positive 4th generation Ag/Ab ELISA assay
* Be stable on ART with a viral load suppressed \<40 copies/mL for a minimum of 2 years
* Have a CD4 count ≥200 cells/mm3 for a minimum of 1 year
* Have a BMI ≥30kg/m2 or have a BMI ≥27kg/m2 and hypertension, dyslipidaemia or type 2 diabetes mellitus
* Understand the study procedures, be able to comply with the study procedures, and voluntarily agree to participate by giving written informed consent for the trial

Exclusion Criteria:

* Subjects unable to comply with the study protocol or unable to self-administer subcutaneous semaglutide
* History of obesity induced by other endocrine disorders: hypothyroidism, Cushing's syndrome, primary and secondary hypogonadism, hypothalamic disorders, polycystic ovary syndrome, insulinoma
* History of obesity induced by use of anti-psychotic medications known to be associated with weight gain (i.e. olanzapine, clozapine).
* Treatment with GLP-1 receptor agonists (including liraglutide, semaglutide or exenatide), dipeptidyl peptidase-4 (DPP-4) inhibitors or insulin within the last 3 months (including saxagliptin, linagliptin, sitagliptin)
* History of severe renal impairment, as defined by a baseline creatinine clearance \<30ml/min
* Individuals with a diagnosis of HIV-associated lipoatrophy/lipodystrophy, based on physician's assessment
* Individuals with severe hepatic impairment (Child Pugh score \>9)
* Subjects with active hepatitis B infection (defined as hepatitis B sAg positive) or hepatitis C (defined as hepatitis C Ab and RNA positive) co-infection
* Any active illness (including AIDS-defining illness) which in the opinion of the investigator precludes participation in the study
* History of cancer (apart from treated Kaposi's Sarcoma) and/or receiving chemotherapy or radiotherapy
* Active illicit intravenous drug use
* Subjects concurrently enrolled in another clinical trial of an investigational medicinal product.
* The investigator may decide that a subject cannot proceed in the study if there is any relevant other abnormal results in the screening assessments
* Subjects with any known or suspected hypersensitivity to semaglutide or any of the excipients of semaglutide
* Subjects on another medicinal product prescribed primarily for weight loss e.g. orlistat (see prohibited/cautioned concomitant medications/therapies section)
* For female subjects: pregnancy or breastfeeding at screening, planning future pregnancies or unwilling to take measures to avoid pregnancy for the duration of the study

Primary outcomes:
measure: Changes in total body weight (in Kg)
timeFrame: 28 weeks
Secondary outcomes:
measure: Proportion of subjects not achieving 5% weight loss from baseline to week 16
timeFrame: 16 weeks
measure: Changes in numbers and function of immune cell subsets
timeFrame: 40 weeks
measure: Changes in quantified viral reservoir in peripheral blood mononuclear cells (PBMCs)
timeFrame: 40 weeks
measure: Changes in gut microbiome composition in stool samples
timeFrame: 40 weeks
measure: Changes in parameters of glucose metabolism in blood samples
timeFrame: 40 weeks
measure: Changes in parameters of lipid metabolism
timeFrame: 40 weeks
measure: Proportion of subjects reporting any adverse event
timeFrame: 40 weeks
measure: Changes in bone mineral density (BMD) and total body composition
timeFrame: 40 weeks
measure: Changes in liver stiffness
timeFrame: 40 weeks
Other outcomes:
Locations:
city: Dublin
country: Ireland
facility: Mater Misericordiae University Hospital
Study officials:
References:
citation: O'Sullivan L, Savinelli S, O'Hare S, Holden S, McHugh C, Mallon P, Doran P. An enhanced participant information leaflet and multimedia intervention to improve the quality of informed consent to a randomised clinical trial enrolling people living with HIV and obesity: a protocol for a Study Within A Trial (SWAT). Trials. 2022 Jan 17;23(1):50. doi: 10.1186/s13063-021-05979-y.