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Class I/II ObesityPhase 4THRIVENCT07592546

Translational Health Research Into Vascular and Neurocognitive Effects of Weight Loss

A Phase 4 study testing semaglutide in people with Class I/II Obesity, run by Alain Dagher at 1 site in Canada.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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?… Read more about this study

Who is it for?
Ages 35 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Class I/II Obesity
What is being tested?
semaglutide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
240 participants
Where
1 siteCanada
Study dates
21 Oct 2026to 1 Jun 2030
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 35 to 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

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

Who cannot join

  • 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;
Show all 13Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Michael Pileggi, M.Sc. contact

514-396-2085

michael.pileggi@mcgill.ca

Filip Morys contact

filip.morys@mcgill.ca

Canada1 site, 1 recruiting

  • The Montreal Neurological Institute-Hospital

    Montreal, Quebec, H3A 2B4

    Alain Dagher, MD

    Recruiting

Other trials in Canada

About this study

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
Read the detailed description

We conducted a priori power calculations (80% power, α=0.05) based on published effect sizes (Cohen's d) for the following measures comparing obese to lean participants: hypothalamic neuroinflammation (d=1.52, required n=8/group; Thaler et al. 2012); cerebral metabolic rate of O₂ (d=1.59, required n=8/group; Anwar et al. 2022); oxygen extraction fraction (OEF) (d=0.67, required n=37/group; Anwar et al. 2022); white matter fractional anisotropy (d=0.61, required n=43/group; Daoust et al. 2021); and for the following measures following bariatric surgery: OEF (d=0.47, required n=37; Anwar et al. 2022); cerebral blood flow (d=0.74, required n=17; Anwar et al. 2022); fALFF (d=1.60, required n=6; Zeighami et al. 2021); cortical thickness (d=0.78, required n=8; Bohon et al. 2018).

Based on the above, we will assume a conservative minimum sample size of 43 per group to detect changes in brain health. In line with previous clinical trials for weight loss, where 88% of patients completed the trial but 83% adhered to the treatment regimen, we will assume a 15% attrition rate. Therefore, the minimum sample size providing adequate statistical power for sex-stratified analyses will be 50 men and 50 women. We will enroll 60 participants per group to account for an additional 20% dropout, for a total target sample of 120. At full enrollment, this will allow us to detect small to medium effects in brain health with over 90% power (Cohen's d=0.30), and sex-stratified analyses will be powered to detect medium effect sizes (Cohen's d=0.40) with 80% power.

If enrollment falls below 100 total participants (50 per group) for feasibility reasons, the sample might be considered insufficient to support confirmatory sex-stratified analyses. In this event, analyses will be conducted in the total sample only. Sex differences may then be examined in an exploratory capacity. This decision rule is pre-specified and will be applied without reference to outcome data.

Anwar, Nareen, Wesley J. Tucker, Nancy Puzziferri, T. Jake Samuel, Vlad G. Zaha, Ildiko Lingvay, Jaime Almandoz, et al. 2022. "Cognition and Brain Oxygen Metabolism Improves after Bariatric Surgery-Induced Weight Loss: A Pilot Study." Frontiers in Endocrinology 13 (December): 954127.

Bohon, Cara, Luis C. Garcia, and John M. Morton. 2018. "Changes in Cerebral Cortical Thickness Related to Weight Loss Following Bariatric Surgery." Obesity Surgery 28 (8): 2578-82.

Daoust, Justine, Joelle Schaffer, Yashar Zeighami, Alain Dagher, Isabel García-García, and Andréanne Michaud. 2021. "White Matter Integrity Differences in Obesity: A Meta-Analysis of Diffusion Tensor Imaging Studies." Neuroscience and Biobehavioral Reviews 129 (October): 133-41.

Thaler, Joshua P., Chun Xia Yi, Ellen A. Schur, Stephan J. Guyenet, Bang H. Hwang, Marcelo O. Dietrich, Xiaolin Zhao, et al. 2012. "Obesity Is Associated with Hypothalamic Injury in Rodents and Humans." The Journal of Clinical Investigation 122 (1): 153.

Zeighami, Yashar, Sylvain Iceta, Mahsa Dadar, Mélissa Pelletier, Mélanie Nadeau, Laurent Biertho, Annie Lafortune, et al. 2021. "Spontaneous Neural Activity Changes after Bariatric Surgery: A Resting-State FMRI Study." NeuroImage 241 (November): 118419.

Being tested
semaglutide
Keywords
weight loss, BMI, Obesity, overweight, obese, semaglutide, Ozempic, Wegovy, GLP-1
Medical subject headings
Weight Loss, Obesity, Overweight

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • semaglutideDrug

    Also called Ozempic, Wegovy

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

Study groups in NCT07592546
Study groupRoleWhat they receive
Overweight Group (BMI 27 - 40 kg/m2)Experimentalsemaglutide
Receives: Drug: semaglutide
Lean group (BMI 20 - 25 kg/m2)No interventionNot described

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Serum C-reactive Protein (CRP)

    Fasting serum CRP concentration (mg/L)

    Measured: Baseline & Change from Baseline

  2. Serum Pro-inflammatory Cytokines (Interleukin-6, TNF-α, Interleukin-1β, and IL-1 Receptor Antagonist)

    Fasting serum concentrations of IL-6, TNF-α, IL-1β, and IL-1 receptor antagonist (all in pg/mL)

    Measured: Baseline & Change from Baseline

  3. Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)

    HOMA-IR is calculated as (fasting glucose [mmol/L] × fasting insulin [μIU/mL]) / 22.5. The resulting dimensionless value estimates insulin resistance; higher values indicate greater insulin resistance.

    Measured: Baseline & Change from Baseline

  4. Fasting Plasma Glucose

    Venous plasma glucose concentration (mmol/L) following an overnight fast

    Measured: Baseline & Change from Baseline

  5. Glycated Hemoglobin A1c (HbA1c)

    Percentage of glycated hemoglobin (%), reflecting mean blood glucose

    Measured: Baseline & Change from Baseline

  6. Serum Leptin

    Fasting serum leptin concentration (ng/mL)

    Measured: Baseline & Change from Baseline

  7. Serum Ghrelin

    Fasting serum ghrelin concentration (pg/mL)

    Measured: Baseline & Change from Baseline

  8. Serum Adiponectin

    Fasting serum adiponectin concentration (μg/mL)

    Measured: Baseline & Change from Baseline

  9. Fasting Serum Insulin

    Fasting serum insulin concentration (μIU/mL)

    Measured: Baseline & Change from Baseline

  10. Serum Glucagon-Like Peptide-1 (GLP-1)

    Serum total GLP-1 concentration (pmol/L)

    Measured: Baseline & Change from Baseline

  11. Serum C-peptide

    Fasting serum C-peptide concentration (nmol/L)

    Measured: Baseline & Change from Baseline

  12. Serum Lipid Panel (Total Cholesterol, HDL Cholesterol, LDL Cholesterol, Triglycerides, and Non-Esterified Fatty Acids [NEFA])

    Fasting serum concentrations of total cholesterol, HDL, LDL, triglycerides, and NEFA (mmol/L)

    Measured: Baseline & Change from Baseline

  13. Serum Apolipoprotein B (ApoB)

    Fasting serum ApoB concentration (g/L)

    Measured: Baseline & Change from Baseline

  14. Red Blood Cell Phospholipid Fatty Acid Composition

    Proportion of individual fatty acid species in red blood cell membrane phospholipids (expressed as % of total fatty acids)

    Measured: Baseline & Change from Baseline

  15. Cerebral Blood Flow as Measured by Pseudo-Continuous Arterial Spin Labeling (pCASL) MRI

    Regional and whole-brain cerebral blood flow (mL/100g/min) derived from pCASL sequences at 3T MRI

    Measured: Baseline & Change from Baseline

  16. Oxygen Extraction Fraction (OEF) as Measured by Quantitative Susceptibility Mapping (QSM) and T2* MRI

    Whole-brain or regional OEF (dimensionless ratio, 0-1) derived from combined QSM and T2* imaging

    Measured: Baseline & Change from Baseline

  17. Cerebral Metabolic Rate of Oxygen (CMRO₂) as Measured by QSM and T2* MRI

    CMRO₂ (μmol/100g/min) estimated from OEF and cerebral blood flow

    Measured: Baseline & Change from Baseline

  18. Cortical Thickness as Measured by Structural MRI

    Mean cortical thickness (mm) derived from T1-weighted

    Measured: Baseline & Change from Baseline

  19. Grey Matter Volume as Measured by Structural MRI

    Regional and total grey matter volume (cm³) derived from T1-weighted structural MRI

    Measured: Baseline & Change from Baseline

  20. Grey Matter Surface Area as Measured by Structural MRI

    Cortical surface area (cm²) derived from T1-weighted structural MRI

    Measured: Baseline & Change from Baseline

  21. White Matter Fractional Anisotropy (FA) as Measured by Diffusion Tensor Imaging (DTI)

    FA (dimensionless, 0-1) derived from DTI; higher FA indicates greater white matter tract coherence

    Measured: Baseline & Change from Baseline

  22. White Matter Mean Diffusivity (MD) as Measured by Diffusion Tensor Imaging (DTI)

    MD (mm²/s) derived from DTI; higher MD may indicate white matter disruption

    Measured: Baseline & Change from Baseline

  23. White Matter Microstructure as Measured by NODDI (intracellular volume fraction [ICVF], isotropic volume fraction [ISOVF], and Orientation Dispersion Index [ODI])

    ICVF, and ISOVF, ODI (dimensionless, 0-1) derived from NODDI modelling of multi-shell diffusion MRI data

    Measured: Baseline & Change from Baseline

  24. White Matter Hyperintensity Volume as Measured by FLAIR MRI

    Total white matter hyperintensity volume (mL) segmented from T2-weighted FLAIR images

    Measured: Baseline & Change from Baseline

  25. Cerebrovascular Reactivity (CVR) as Measured by BOLD fMRI with End-Tidal CO₂ (EtCO₂) Challenge

    CVR (expressed as % BOLD signal change per mmHg EtCO₂) derived from BOLD fMRI acquired during a hypercapnic EtCO₂ challenge

    Measured: Baseline & Change from Baseline

  26. Neuroinflammation proxy as Measured by T2* relaxation times

    Milliseconds (ms)

    Measured: Baseline & Change from Baseline

  27. Neuromelanin Contrast Ratio in the Substantia Nigra as Measured by Neuromelanin-Sensitive MRI

    Ratio of T1 signal intensity in the substantia nigra pars compacta relative to a reference region (dimensionless), used as an indirect in vivo measure of neuromelanin content

    Measured: Baseline & Change from Baseline

  28. Intracranial Artery Lumen Diameter as Measured by Time-of-Flight MRA

    Lumen diameter (mm) measured at standardized segments of the ICA, MCA, basilar, and vertebral arteries using 3D TOF-MRA at 3T

    Measured: Baseline & Change from Baseline

  29. Body Mass Index (BMI)

    BMI (kg/m²) calculated from measured height (m) and body weight (kg)

    Measured: Baseline & Change from Baseline

  30. Waist Circumference, Hip Circumference

    circumference (cm)

    Measured: Baseline & Change from Baseline

  31. Waist-to-height ratio, Waist-to-hip ratio

    Unitless

    Measured: Baseline & Change from Baseline

  32. Visceral Adipose Tissue as Measured by MRI

    Visceral adipose tissue volume (mL) quantified by MRI Dixon sequence and Bioimpedance Analysis

    Measured: Baseline & Change from Baseline

  33. Subcutaneous Adipose Tissue as Measured by MRI

    Subcutaneous adipose tissue volume (mL) quantified by MRI

    Measured: Baseline & Change from Baseline

  34. Body Composition

    Whole-body fat as a percentage of total body mass (%), lean mass tissue, muscle mass measured by BIA

    Measured: Baseline & Change from Baseline

Secondary outcomes (15)

  1. Delay Discounting Task Score (Impulsive Choice)

    The Delay Discounting Task quantifies impulsive choice by measuring preference for smaller immediate versus larger delayed rewards. The discounting rate (k value, log-transformed) is the primary output; higher k values indicate greater impulsivity.

    Measured: Baseline & Change from Baseline

  2. Penn Line Orientation Test Score (Visual Processing)

    The Penn Line Orientation Test (PLOT) assesses visuospatial processing by asking participants to match line orientations. Higher scores indicate better visual processing performance.

    Measured: Baseline & Change from Baseline

  3. Penn Progressive Matrices Score (Fluid Intelligence)

    The Penn Progressive Matrices is a nonverbal test of fluid reasoning and abstract problem-solving. Higher scores indicate greater fluid intelligence.

    Measured: Baseline & Change from Baseline

  4. Oral Reading Recognition Test Score (Language Ability)

    The Oral Reading Recognition Test assesses language ability and reading recognition. Scores are reported as raw scores; higher scores indicate better language performance.

    Measured: Baseline & Change from Baseline

  5. Penn Word Memory Test Score (Episodic Memory)

    The Penn Word Memory Test assesses verbal episodic memory via a word recognition paradigm. Performance is reported as percentage of words correctly recognized (0-100%); higher values indicate better episodic memory.

    Measured: Baseline & Change from Baseline

  6. Relational Memory Task Score (Executive Function and Attention)

    The Relational Task assesses relational reasoning and executive attention. Performance is reported as [% correct / reaction time in ms]; [higher accuracy / lower reaction time] indicates better performance.

    Measured: Baseline & Change from Baseline

  7. Montreal Cognitive Assessment (MoCA) Total Score

    The MoCA is a brief cognitive screening tool assessing multiple domains including memory, attention, language, and visuospatial ability. Scores range from 0 to 30; higher scores indicate better global cognitive function.

    Measured: Baseline & Change from Baseline

  8. Patient Health Questionnaire-9 (PHQ-9) Depression Score

    The PHQ-9 is a 9-item validated self-report questionnaire measuring depressive symptom severity over the preceding 2 weeks. Scores range from 0 to 27; higher scores indicate greater depressive symptom severity.

    Measured: Baseline & Change from Baseline

  9. Mean Daily Energy Intake, fat, carbohydrate, sugar, protein intake, saturated fatty acids intake as Assessed by 3-Day Food Record.

    Daily energy intake from different macronutrients (kcal/day) derived from a 3-day food record and.

    Measured: Baseline & Change from Baseline

  10. Percentage of calories derived from each of NOVA food classification categories

    Units: Percentage (%)

    Measured: Baseline & Change from Baseline

  11. Healthy Eating Index

    The Healthy Eating Index (HEI) measures diet quality on a scale of 0 to 100, where 100 indicates perfect alignment with the Dietary Guidelines for Americans

    Measured: Baseline & Change from Baseline

  12. Fat Taste Preference Score

    Geometric average of a preferred solution from a Monell 2-series forced choice test.

    Measured: Baseline & Change from Baseline

  13. Sweet Taste Preference Score

    Geometric average of a preferred solution from a Monell 2-series forced choice test.

    Measured: Baseline & Change from Baseline

  14. Working memory capacity

    Digits remembered on the digit span and digit span backwards task

    Measured: Baseline & Change from Baseline

  15. Reinforcement learning outcomes

    Choose-A accuracy (reward learning)

    Proportion of test-phase trials on which participants select stimulus A (the most frequently rewarded stimulus, 80% positive feedback) when paired with novel stimuli, indexing the bias to learn from positive feedback / approach the best option.

    Avoid-B accuracy (punishment learning)

    Proportion of test-phase trials on which participants avoid stimulus B (the most frequently punished stimulus, 80% negative feedback) when paired with novel stimuli, indexing the bias to learn from negative feedback / avoid the worst option.

    Measured: Baseline & Change from Baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 May 2026
  2. Study start21 Oct 2026
  3. Primary completion1 Dec 2028 (estimated)
  4. Study completion1 Jun 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
The population selected for this trial includes adults aged 35 to 55 years with overweight or obesity (BMI 27-40 kg/m²) and an age- and sex-matched lean control group (BMI 20-25 kg/m²).
Masking
None (open label)
Enrolment
240 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07592546
Sponsor's protocol ID
THRIVE
Acronym
THRIVE
Status last verified
Oct 2026
First submitted
3 May 2026
Last updated
26 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: All anonymised and de-identified IPD (not biological samples) will be available to researchers on a case by case basis after trial completion.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing semaglutide in people with Class I/II Obesity, run by Alain Dagher at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Michael Pileggi, M.Sc. (514-396-2085, michael.pileggi@mcgill.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Serum C-reactive Protein (CRP) (time frame: Baseline & Change from Baseline). The study lists 34 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07592546.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.

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