Semaglutide's Efficacy in Achieving Weight Loss for Those With HIV

Obesity Clinical Trial

— SWIFT  

Official title:

Semaglutide's Efficacy in Achieving Weight Loss for Those With HIV

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04174755
• Other study ID #: SWIFT Study
• Status: Recruiting
• Phase: N/A
• Start date: June 22, 2022
• Est. completion date: January 2025

Study information

• Verified date: October 2023
• Source: University College Dublin
• Contact: Stefano Savinelli, MD
• Phone: +3532215014
• Email: stefano.savinelli1[@]ucd.ie
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: January 2025
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• HIV-1-infection
• Obesity
• Weight Loss

Intervention

Drug:
• Semaglutide Injectable Product
Semaglutide 0.25 mg subcutaneously once weekly for 4 weeks, then Semaglutide 0.5 mg subcutaneously once weekly for 4 weeks, then Semaglutide 1 mg subcutaneously once weekly for 20 weeks. Total treatment duration 28 weeks.

Behavioral:
• Standard of care
Diet and exercise advice for 40 weeks

Locations

Country	Name	City	State
Ireland	Mater Misericordiae University Hospital	Dublin

Sponsors (3)

Lead Sponsor	Collaborator
University College Dublin	Rush University Medical Center, University of Copenhagen

Country where clinical trial is conducted

Ireland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in total body weight (in Kg)	Between-group differences in percent change from baseline to week 28 in total body weight	28 weeks
Secondary	Proportion of subjects not achieving 5% weight loss from baseline to week 16	Between-group differences in number of subjects who do not achieve a 5% weight loss (in Kg) from baseline to week 16	16 weeks
Secondary	Changes in numbers and function of immune cell subsets	Between-group differences in percent change from baseline in numbers and functions of immune cells subsets (NK cells, MAIT cells, T-cells and Monocytes) as assessed through flow cytometry in a single assay	40 weeks
Secondary	Changes in quantified viral reservoir in peripheral blood mononuclear cells (PBMCs)	Between-group differences in percent change from baseline in HIV pro-viral DNA and cell-associated RNA (CA-RNA), measured in PBMCs (copies/mL)	40 weeks
Secondary	Changes in gut microbiome composition in stool samples	Between-group differences in percent change from baseline in gut microbiome composition (% prevalence of different microbial species) as assessed through molecular techniques in stool samples	40 weeks
Secondary	Changes in parameters of glucose metabolism in blood samples	Between-group differences in percent change from baseline in blood glucose levels (in mmol/L), HbA1c (in mmol/mol) and insulin levels (in pmol/L)	40 weeks
Secondary	Changes in parameters of lipid metabolism	Between-group differences in percent change from baseline in lipid profile: total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides (all in mmol/L)	40 weeks
Secondary	Proportion of subjects reporting any adverse event	Between-group differences in the number of subjects reporting any type of adverse event, including serious adverse events and suspected unexpected serious adverse reactions	40 weeks
Secondary	Changes in bone mineral density (BMD) and total body composition	Between-group differences in percent change from baseline in lumbar spine and hip BMD and total body composition (% fat mass and lean mass) as assessed through DXA scan	40 weeks
Secondary	Changes in liver stiffness	Between-group differences in percent change from baseline in liver stiffness (measured in kPa) as assessed thourgh liver elastography	40 weeks