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

• ClinicalTrials.gov Identifier: NCT04174755
• Recruitment Status: Recruiting
• First Posted: November 22, 2019
• Last Update Posted: October 24, 2023
• Sponsor: University College Dublin
• Collaborators: University of Copenhagen; Rush University Medical Center
• Information provided by (Responsible Party): Patrick Mallon, University College Dublin

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Obesity; HIV-1-infection	Drug: Semaglutide Injectable Product; Behavioral: Standard of care	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Semaglutide's Efficacy in Achieving Weight Loss for Those With HIV
• Actual Study Start Date: June 22, 2022
• Estimated Primary Completion Date: November 2024
• Estimated Study Completion Date: January 2025

Arms and Interventions

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 Name: Ozempic; Behavioral: Standard of care; Diet and exercise advice for 40 weeks; Other Name: Diet and exercise
Standard of care alone	Behavioral: Standard of care; Diet and exercise advice for 40 weeks; Other Name: Diet and exercise

Outcome Measures

Primary Outcome Measures :

1. Changes in total body weight (in Kg) [ Time Frame: 28 weeks ]
   Between-group differences in percent change from baseline to week 28 in total body weight

Secondary Outcome Measures :

1. Proportion of subjects not achieving 5% weight loss from baseline to week 16 [ Time Frame: 16 weeks ]
   Between-group differences in number of subjects who do not achieve a 5% weight loss (in Kg) from baseline to week 16
2. Changes in numbers and function of immune cell subsets [ Time Frame: 40 weeks ]
   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
3. Changes in quantified viral reservoir in peripheral blood mononuclear cells (PBMCs) [ Time Frame: 40 weeks ]
   Between-group differences in percent change from baseline in HIV pro-viral DNA and cell-associated RNA (CA-RNA), measured in PBMCs (copies/mL)
4. Changes in gut microbiome composition in stool samples [ Time Frame: 40 weeks ]
   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
5. Changes in parameters of glucose metabolism in blood samples [ Time Frame: 40 weeks ]
   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)
6. Changes in parameters of lipid metabolism [ Time Frame: 40 weeks ]
   Between-group differences in percent change from baseline in lipid profile: total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides (all in mmol/L)
7. Proportion of subjects reporting any adverse event [ Time Frame: 40 weeks ]
   Between-group differences in the number of subjects reporting any type of adverse event, including serious adverse events and suspected unexpected serious adverse reactions
8. Changes in bone mineral density (BMD) and total body composition [ Time Frame: 40 weeks ]
   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
9. Changes in liver stiffness [ Time Frame: 40 weeks ]
   Between-group differences in percent change from baseline in liver stiffness (measured in kPa) as assessed thourgh liver elastography

Eligibility Criteria

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

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

Contacts and Locations

Contacts

Contact: Stefano Savinelli, MD; +3532215014; stefano.savinelli1@ucd.ie

Locations

Ireland

Mater Misericordiae University Hospital; Recruiting

Dublin, Ireland, D07 R2WY

Contact: Aoife Cotter, PhD aoife.cotter@ucd.ie

Sponsors and Collaborators

University College Dublin

University of Copenhagen

Rush University Medical Center

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Patrick Mallon, Professor of Microbial Diseases, University College Dublin
• ClinicalTrials.gov Identifier: NCT04174755
• Other Study ID Numbers: SWIFT Study
• First Posted: November 22, 2019
• Last Update Posted: October 24, 2023
• Last Verified: October 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Patrick Mallon, University College Dublin:

obesity; HIV; weight loss; GLP-1 analogue; immune activation; viral reservoir; gut microbiome

Additional relevant MeSH terms:

Weight Loss; Body Weight; Body Weight Changes; Semaglutide; Glucagon-Like Peptide-1 Receptor Agonists; Hypoglycemic Agents; Physiological Effects of Drugs