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

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.

Study Overview

• Status: Recruiting
• Conditions: Obesity; HIV-1-infection
• Intervention / Treatment: Drug: Semaglutide Injectable Product; Behavioral: Standard of care

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.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Stefano Savinelli, MD; Phone Number: +3532215014; Email: stefano.savinelli1@ucd.ie

Study Locations

• Ireland
  • Dublin, Ireland, D07 R2WY
    • Recruiting
    • Mater Misericordiae University Hospital
    • Contact: Aoife Cotter, PhD; Email: aoife.cotter@ucd.ie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Semaglutide 0.25/0.5/1 mg plus standard of care	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.; Other Names: Ozempic; Behavioral: Standard of care; Diet and exercise advice for 40 weeks; Other Names: Diet and exercise
Other: Standard of care alone	Behavioral: Standard of care; Diet and exercise advice for 40 weeks; Other Names: Diet and exercise

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: University College Dublin
• Collaborators: University of Copenhagen; Rush University Medical Center

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2022
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: November 6, 2019
• First Submitted That Met QC Criteria: November 20, 2019
• First Posted (Actual): November 22, 2019

Study Record Updates

• Last Update Posted (Actual): October 24, 2023
• Last Update Submitted That Met QC Criteria: October 23, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: HIV; obesity; weight loss; gut microbiome; immune activation; GLP-1 analogue; viral reservoir
• Additional Relevant MeSH Terms: Body Weight; Body Weight Changes; Weight Loss
• Other Study ID Numbers: SWIFT Study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No