Recruiting
Phase 4

Semaglutide

Sponsor:

Alain Dagher

Code:

NCT07592546

Conditions

Class I/II Obesity

Eligibility Criteria

Sex: All

Age: 35 - 55

Healthy Volunteers: Accepted

Interventions

semaglutide

Study Details

Brief summary:

The goal of this clinical trial is to learn about the nature of brain abnormalities associated with excess body fat in healthy adults aged 35-55. The main questions it aims to answer are:

  • Will excessive fat be associated with brain abnormalities on MRI measures?
  • Will weight loss change brain health on MRI measures?

Participants will:

  • Self-administer study drug, semaglutide, once a week for 80 weeks
  • Complete metabolic and basic body measurements
  • Complete cognitive, mood, and dietary assessments
  • Complete questionnaires
  • Undergo MRIs

Conditions

Class I/II Obesity

Study ID

NCT07592546

Start date

Oct 21, 2026

Status verified date

Oct, 2026

Completion date

Jun 1, 2030

Anticipated

Primary completion date

Dec 1, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 35 - 55

Healthy Volunteers: Accepted

Inclusion Criteria:

Key inclusion criteria for obese group:

  • Individuals of age 35-55 years with BMI 27 - 40 kg/m2
  • Able to provide informed consent
  • Willing to self-inject semaglutide and follow study procedures for its entire duration.

Key inclusion criteria for lean control group:

  • Individuals of age 35-55 years with BMI 20 - 25 kg/m2
  • Able to provide informed consent

Exclusion Criteria for both groups:

  • Current type 2 diabetes mellitus;
  • Neurological disorders affecting the CNS;
  • History or family history of medullary thyroid carcinoma or MEN2 syndrome
  • CNS-active medications (outside of medications used to control psychiatric disorders);
  • Poorly controlled psychiatric disorders including major depression or previous suicidality;
  • Class III obesity (BMI>40 or BMI>35 with complications) as these individuals are eligible for bariatric surgery in Canada and will be referred for appropriate medical care;
  • Clinical safety blood measures indicative of a medical issue.
  • History of weight change > 5 kg in past 90 days;
  • History of pancreatitis
  • Previous or planned bariatric surgery;
  • Use of another weight loss medication during trial participation and within 90 days before enrolment;
  • History of serious medical illness, monogenic obesity, uncontrolled hypertension (sBP>160 mmHg, dBP>100 mmHg), active malignancy, illicit substance use, cigarette smoking, diagnosed eating disorder, as listed in the study protocol associated with; Other obesity comorbidities, e.g. hypertension, pre-diabetes (HbA1C = 6% to 6.4%), hyperlipidemia, controlled depressive disorder or anxiety, ADHD, and polycystic ovary syndrome, will not be exclusion criteria as this would reduce the representativeness of our sample.
  • Female subjects of childbearing potential (i.e., a premenopausal female capable of becoming pregnant) are eligible to enroll if they are either sexually inactive/abstinent or using an effective contraceptive from screening until 4 weeks after the last dose. Medically accepted contraception are hormonal implants, hormonal patches, IDU, diaphragm and spermicide, cervical cape with spermicide, and condom with spermicide.

Study Design

Enrollment

240 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Overweight Group (BMI 27 - 40 kg/m2)

semaglutide

no intervention: Lean group (BMI 20 - 25 kg/m2)

Interventions

semaglutide

Treatment will be given for 80 weeks. Dose will be escalated from 0.25 mg to a max of 2.4 mg per week.

Primary outcome measure

  • Serum C-reactive Protein (CRP) [ Time Frame: Baseline & Change from Baseline ]
  • Serum Pro-inflammatory Cytokines (Interleukin-6, TNF-α, Interleukin-1β, and IL-1 Receptor Antagonist) [ Time Frame: Baseline & Change from Baseline ]
  • Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) [ Time Frame: Baseline & Change from Baseline ]
  • Fasting Plasma Glucose [ Time Frame: Baseline & Change from Baseline ]
  • Glycated Hemoglobin A1c (HbA1c) [ Time Frame: Baseline & Change from Baseline ]
  • Serum Leptin [ Time Frame: Baseline & Change from Baseline ]
  • Serum Ghrelin [ Time Frame: Baseline & Change from Baseline ]
  • Serum Adiponectin [ Time Frame: Baseline & Change from Baseline ]
  • Fasting Serum Insulin [ Time Frame: Baseline & Change from Baseline ]
  • Serum Glucagon-Like Peptide-1 (GLP-1) [ Time Frame: Baseline & Change from Baseline ]
  • Serum C-peptide [ Time Frame: Baseline & Change from Baseline ]
  • Serum Lipid Panel (Total Cholesterol, HDL Cholesterol, LDL Cholesterol, Triglycerides, and Non-Esterified Fatty Acids [NEFA]) [ Time Frame: Baseline & Change from Baseline ]
  • Serum Apolipoprotein B (ApoB) [ Time Frame: Baseline & Change from Baseline ]
  • Red Blood Cell Phospholipid Fatty Acid Composition [ Time Frame: Baseline & Change from Baseline ]
  • Cerebral Blood Flow as Measured by Pseudo-Continuous Arterial Spin Labeling (pCASL) MRI [ Time Frame: Baseline & Change from Baseline ]
  • Oxygen Extraction Fraction (OEF) as Measured by Quantitative Susceptibility Mapping (QSM) and T2* MRI [ Time Frame: Baseline & Change from Baseline ]
  • Cerebral Metabolic Rate of Oxygen (CMRO₂) as Measured by QSM and T2* MRI [ Time Frame: Baseline & Change from Baseline ]
  • Cortical Thickness as Measured by Structural MRI [ Time Frame: Baseline & Change from Baseline ]
  • Grey Matter Volume as Measured by Structural MRI [ Time Frame: Baseline & Change from Baseline ]
  • Grey Matter Surface Area as Measured by Structural MRI [ Time Frame: Baseline & Change from Baseline ]
  • White Matter Fractional Anisotropy (FA) as Measured by Diffusion Tensor Imaging (DTI) [ Time Frame: Baseline & Change from Baseline ]
  • White Matter Mean Diffusivity (MD) as Measured by Diffusion Tensor Imaging (DTI) [ Time Frame: Baseline & Change from Baseline ]
  • White Matter Microstructure as Measured by NODDI (intracellular volume fraction [ICVF], isotropic volume fraction [ISOVF], and Orientation Dispersion Index [ODI]) [ Time Frame: Baseline & Change from Baseline ]
  • White Matter Hyperintensity Volume as Measured by FLAIR MRI [ Time Frame: Baseline & Change from Baseline ]
  • Cerebrovascular Reactivity (CVR) as Measured by BOLD fMRI with End-Tidal CO₂ (EtCO₂) Challenge [ Time Frame: Baseline & Change from Baseline ]
  • Neuroinflammation proxy as Measured by T2* relaxation times [ Time Frame: Baseline & Change from Baseline ]
  • Neuromelanin Contrast Ratio in the Substantia Nigra as Measured by Neuromelanin-Sensitive MRI [ Time Frame: Baseline & Change from Baseline ]
  • Intracranial Artery Lumen Diameter as Measured by Time-of-Flight MRA [ Time Frame: Baseline & Change from Baseline ]
  • Body Mass Index (BMI) [ Time Frame: Baseline & Change from Baseline ]
  • Waist Circumference, Hip Circumference [ Time Frame: Baseline & Change from Baseline ]
  • Waist-to-height ratio, Waist-to-hip ratio [ Time Frame: Baseline & Change from Baseline ]
  • Visceral Adipose Tissue as Measured by MRI [ Time Frame: Baseline & Change from Baseline ]
  • Subcutaneous Adipose Tissue as Measured by MRI [ Time Frame: Baseline & Change from Baseline ]
  • Body Composition [ Time Frame: Baseline & Change from Baseline ]

Central Contacts and Locations

Central contacts

Michael Pileggi, M.Sc.

514-396-2085michael.pileggi@mcgill.ca

Filip Morys

filip.morys@mcgill.ca

Locations

The Montreal Neurological Institute-Hospital

Recruiting

Montreal, Quebec, Canada, H3A 2B4

Principal Investigator:

Alain Dagher, MD

More Information

Sponsor

Alain Dagher

Last update posted

Oct 26, 2026

Last verified

Oct, 2026

Keywords

  • weight loss
  • BMI
  • Obesity
  • overweight
  • obese
  • semaglutide
  • Ozempic
  • Wegovy
  • GLP-1

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-27. This information was provided to ClinicalTrials.gov by Alain Dagher on 2026-10-26. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.