THRIVE

Not yet recruitingPhase 4

Translational Health Research Into Vascular and Neurocognitive Effects of Weight Loss

Lead sponsor

Alain Dagher

Asset

Semaglutide

GLP-1 agonist

Listed sites

Recruiting sites

Estimated enrollment

240

Study population

Healthy volunteers, Obesity / overweight

Eligibility highlights

•BMI 27-40

Primary endpoints

•Hs-CRP, change•Serum Pro-inflammatory Cytokines•HOMA-IR (insulin sensitivity)

Registered trial locations

Locations reported to ClinicalTrials.gov for this trial snapshot. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT07592546

Org study IDTHRIVE

Timeline

Milestones

Study first posted2026-05-18actual

Last update posted2026-05-22actual

Study start2026-08-01estimated

Primary completion2028-12-01estimated

Study completion2030-06-01estimated

Assets

Investigational agents

Semaglutide

Who this study enrolls

Healthy volunteersObesity / overweight

Who can enroll

Minimum age35 Years

Maximum age55 Years

SexAll

Healthy volunteersAccepted

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.

Endpoints (47)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Other clinical outcomes

Other (unclassified)

Cardiometabolic biomarkers

Weight & body composition

Glycemic / diabetes

Patient-reported / QoL

Weight & body composition

6 endpoints

Primary/protocol endpoint

Body Mass Index (BMI)

Time frame:Baseline & Change from Baseline

BMI, change

change from baseline, improvement

Primary/protocol endpoint

Waist Circumference, Hip Circumference

Time frame:Baseline & Change from Baseline

Waist circumference, change

change from baseline, improvement

Primary/protocol endpoint

Waist-to-height ratio, Waist-to-hip ratio

Time frame:Baseline & Change from Baseline

change from baseline, improvement

Primary/protocol endpoint

Visceral Adipose Tissue as Measured by MRI

Time frame:Baseline & Change from Baseline

Visceral fat, change

change from baseline, improvement

Primary/protocol endpoint

Subcutaneous Adipose Tissue as Measured by MRI

Time frame:Baseline & Change from Baseline

Subcutaneous fat, change

change from baseline, improvement

Primary/protocol endpoint

Body Composition

Time frame:Baseline & Change from Baseline

Total fat mass

change from baseline, improvement

componentsTotal fat mass, Lean mass

Glycemic / diabetes

5 endpoints

Primary/protocol endpoint

Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)

Time frame:Baseline & Change from Baseline

HOMA-IR (insulin sensitivity)

change from baseline, improvement

Primary/protocol endpoint

Fasting Plasma Glucose

Time frame:Baseline & Change from Baseline

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Primary/protocol endpoint

Glycated Hemoglobin A1c (HbA1c)

Time frame:Baseline & Change from Baseline

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Primary/protocol endpoint

Fasting Serum Insulin

Time frame:Baseline & Change from Baseline

change from baseline, improvement

Primary/protocol endpoint

Serum C-peptide

Time frame:Baseline & Change from Baseline

C-peptide AUC

change from baseline, improvement

Cardiometabolic biomarkers

7 endpoints

Primary/protocol endpoint

Serum C-reactive Protein (CRP)

Time frame:Baseline & Change from Baseline

hs-CRP, change

change from baseline, improvement

LOINC 30522-7

Primary/protocol endpoint

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

Time frame:Baseline & Change from Baseline

change from baseline, improvement

Primary/protocol endpoint

Serum Leptin

Time frame:Baseline & Change from Baseline

Leptin, change

change from baseline, improvement

Primary/protocol endpoint

Serum Ghrelin

Time frame:Baseline & Change from Baseline

change from baseline, improvement

Primary/protocol endpoint

Serum Adiponectin

Time frame:Baseline & Change from Baseline

Adiponectin, change

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline & Change from Baseline

change from baseline, improvement

componentsTotal cholesterol, change, HDL-C, change, LDL-C, change, Triglycerides, change, Free fatty acids, change

Primary/protocol endpoint

Serum Apolipoprotein B (ApoB)

Time frame:Baseline & Change from Baseline

ApoB, change

change from baseline, improvement

Patient-reported / QoL

1 endpoint

Secondary/protocol endpoint

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

Time frame:Baseline & Change from Baseline

change from baseline, improvement

Other clinical outcomes

19 endpoints

Primary/protocol endpoint

Cortical Thickness as Measured by Structural MRI

Time frame:Baseline & Change from Baseline

change from baseline, descriptive

Primary/protocol endpoint

Grey Matter Volume as Measured by Structural MRI

Time frame:Baseline & Change from Baseline

change from baseline, descriptive

Primary/protocol endpoint

Grey Matter Surface Area as Measured by Structural MRI

Time frame:Baseline & Change from Baseline

change from baseline, descriptive

Primary/protocol endpoint/low confidence

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

Time frame:Baseline & Change from Baseline

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline & Change from Baseline

change from baseline, descriptive

Primary/protocol endpoint

White Matter Hyperintensity Volume as Measured by FLAIR MRI

Time frame:Baseline & Change from Baseline

change from baseline, improvement

Primary/protocol endpoint

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

Time frame:Baseline & Change from Baseline

ratio, descriptive

Primary/protocol endpoint/low confidence

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

Time frame:Baseline & Change from Baseline

change from baseline, descriptive

Secondary/protocol endpoint

Delay Discounting Task Score (Impulsive Choice)

Time frame:Baseline & Change from Baseline

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Penn Line Orientation Test Score (Visual Processing)

Time frame:Baseline & Change from Baseline

change from baseline, improvement

Secondary/protocol endpoint

Penn Progressive Matrices Score (Fluid Intelligence)

Time frame:Baseline & Change from Baseline

change from baseline, improvement

Secondary/protocol endpoint

Oral Reading Recognition Test Score (Language Ability)

Time frame:Baseline & Change from Baseline

change from baseline, improvement

Secondary/protocol endpoint

Penn Word Memory Test Score (Episodic Memory)

Time frame:Baseline & Change from Baseline

change from baseline, improvement

Secondary/protocol endpoint

Relational Memory Task Score (Executive Function and Attention)

Time frame:Baseline & Change from Baseline

change from baseline, improvement

Secondary/protocol endpoint

Montreal Cognitive Assessment (MoCA) Total Score

Time frame:Baseline & Change from Baseline

change from baseline, improvement

Secondary/protocol endpoint

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

Time frame:Baseline & Change from Baseline

change from baseline, descriptive

Secondary/protocol endpoint/low confidence

Healthy Eating Index

Time frame:Baseline & Change from Baseline

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Fat Taste Preference Score

Time frame:Baseline & Change from Baseline

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Sweet Taste Preference Score

Time frame:Baseline & Change from Baseline

change from baseline, improvement

Other (unclassified)

9 endpoints

Primary/protocol endpoint/low confidence

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

Time frame:Baseline & Change from Baseline

concentration, descriptive

Primary/protocol endpoint/low confidence

Red Blood Cell Phospholipid Fatty Acid Composition

Time frame:Baseline & Change from Baseline

descriptive

Primary/protocol endpoint/low confidence

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

Time frame:Baseline & Change from Baseline

change from baseline, descriptive

Primary/protocol endpoint/low confidence

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

Time frame:Baseline & Change from Baseline

change from baseline, descriptive

Primary/protocol endpoint/low confidence

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

Time frame:Baseline & Change from Baseline

change from baseline, descriptive

Primary/protocol endpoint/low confidence

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

change from baseline, descriptive

Primary/protocol endpoint/low confidence

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

Time frame:Baseline & Change from Baseline

change from baseline, descriptive

Primary/protocol endpoint/low confidence

Neuroinflammation proxy as Measured by T2* relaxation times

Time frame:Baseline & Change from Baseline

change from baseline, descriptive

Secondary/protocol endpoint/low confidence

Percentage of calories derived from each of NOVA food classification categories

Time frame:Baseline & Change from Baseline

percent change from baseline, descriptive

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 6, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 6, 2026 snapshot.