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Translational Health Research Into Vascular and Neurocognitive Effects of Weight Loss (THRIVE)

23. juni 2026 oppdatert av: Alain Dagher

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

Studieoversikt

Status

Har ikke rekruttert ennå

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

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.

Studietype

Intervensjonell

Registrering (Antatt)

240

Fase

  • Fase 4

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Studer Kontakt Backup

Studiesteder

  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H3A 2B4
        • The Montreal Neurological Institute-Hospital
        • Hovedetterforsker:
          • Alain Dagher, MD

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

  • Voksen

Tar imot friske frivillige

Ja

Beskrivelse

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.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Overweight Group (BMI 27 - 40 kg/m2)
semaglutide
Legemiddel: 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.
Andre navn:
  • Ozempisk
  • Wegovy
Ingen inngripen: Lean group (BMI 20 - 25 kg/m2)

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Serum C-reactive Protein (CRP)
Tidsramme: Baseline & Change from Baseline
Fasting serum CRP concentration (mg/L)
Baseline & Change from Baseline
Serum Pro-inflammatory Cytokines (Interleukin-6, TNF-α, Interleukin-1β, and IL-1 Receptor Antagonist)
Tidsramme: Baseline & Change from Baseline
Fasting serum concentrations of IL-6, TNF-α, IL-1β, and IL-1 receptor antagonist (all in pg/mL)
Baseline & Change from Baseline
Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)
Tidsramme: Baseline & Change from Baseline
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.
Baseline & Change from Baseline
Fasting Plasma Glucose
Tidsramme: Baseline & Change from Baseline
Venous plasma glucose concentration (mmol/L) following an overnight fast
Baseline & Change from Baseline
Glycated Hemoglobin A1c (HbA1c)
Tidsramme: Baseline & Change from Baseline
Percentage of glycated hemoglobin (%), reflecting mean blood glucose
Baseline & Change from Baseline
Serum Leptin
Tidsramme: Baseline & Change from Baseline
Fasting serum leptin concentration (ng/mL)
Baseline & Change from Baseline
Serum Ghrelin
Tidsramme: Baseline & Change from Baseline
Fasting serum ghrelin concentration (pg/mL)
Baseline & Change from Baseline
Serum Adiponectin
Tidsramme: Baseline & Change from Baseline
Fasting serum adiponectin concentration (μg/mL)
Baseline & Change from Baseline
Fasting Serum Insulin
Tidsramme: Baseline & Change from Baseline
Fasting serum insulin concentration (μIU/mL)
Baseline & Change from Baseline
Serum Glucagon-Like Peptide-1 (GLP-1)
Tidsramme: Baseline & Change from Baseline
Serum total GLP-1 concentration (pmol/L)
Baseline & Change from Baseline
Serum C-peptide
Tidsramme: Baseline & Change from Baseline
Fasting serum C-peptide concentration (nmol/L)
Baseline & Change from Baseline
Serum Lipid Panel (Total Cholesterol, HDL Cholesterol, LDL Cholesterol, Triglycerides, and Non-Esterified Fatty Acids [NEFA])
Tidsramme: Baseline & Change from Baseline
Fasting serum concentrations of total cholesterol, HDL, LDL, triglycerides, and NEFA (mmol/L)
Baseline & Change from Baseline
Serum Apolipoprotein B (ApoB)
Tidsramme: Baseline & Change from Baseline
Fasting serum ApoB concentration (g/L)
Baseline & Change from Baseline
Red Blood Cell Phospholipid Fatty Acid Composition
Tidsramme: Baseline & Change from Baseline
Proportion of individual fatty acid species in red blood cell membrane phospholipids (expressed as % of total fatty acids)
Baseline & Change from Baseline
Cerebral Blood Flow as Measured by Pseudo-Continuous Arterial Spin Labeling (pCASL) MRI
Tidsramme: Baseline & Change from Baseline
Regional and whole-brain cerebral blood flow (mL/100g/min) derived from pCASL sequences at 3T MRI
Baseline & Change from Baseline
Oxygen Extraction Fraction (OEF) as Measured by Quantitative Susceptibility Mapping (QSM) and T2* MRI
Tidsramme: Baseline & Change from Baseline
Whole-brain or regional OEF (dimensionless ratio, 0-1) derived from combined QSM and T2* imaging
Baseline & Change from Baseline
Cerebral Metabolic Rate of Oxygen (CMRO₂) as Measured by QSM and T2* MRI
Tidsramme: Baseline & Change from Baseline
CMRO₂ (μmol/100g/min) estimated from OEF and cerebral blood flow
Baseline & Change from Baseline
Cortical Thickness as Measured by Structural MRI
Tidsramme: Baseline & Change from Baseline
Mean cortical thickness (mm) derived from T1-weighted
Baseline & Change from Baseline
Grey Matter Volume as Measured by Structural MRI
Tidsramme: Baseline & Change from Baseline
Regional and total grey matter volume (cm³) derived from T1-weighted structural MRI
Baseline & Change from Baseline
Grey Matter Surface Area as Measured by Structural MRI
Tidsramme: Baseline & Change from Baseline
Cortical surface area (cm²) derived from T1-weighted structural MRI
Baseline & Change from Baseline
White Matter Fractional Anisotropy (FA) as Measured by Diffusion Tensor Imaging (DTI)
Tidsramme: Baseline & Change from Baseline
FA (dimensionless, 0-1) derived from DTI; higher FA indicates greater white matter tract coherence
Baseline & Change from Baseline
White Matter Mean Diffusivity (MD) as Measured by Diffusion Tensor Imaging (DTI)
Tidsramme: Baseline & Change from Baseline
MD (mm²/s) derived from DTI; higher MD may indicate white matter disruption
Baseline & Change from Baseline
White Matter Microstructure as Measured by NODDI (intracellular volume fraction [ICVF], isotropic volume fraction [ISOVF], and Orientation Dispersion Index [ODI])
Tidsramme: Baseline & Change from Baseline
ICVF, and ISOVF, ODI (dimensionless, 0-1) derived from NODDI modelling of multi-shell diffusion MRI data
Baseline & Change from Baseline
White Matter Hyperintensity Volume as Measured by FLAIR MRI
Tidsramme: Baseline & Change from Baseline
Total white matter hyperintensity volume (mL) segmented from T2-weighted FLAIR images
Baseline & Change from Baseline
Cerebrovascular Reactivity (CVR) as Measured by BOLD fMRI with End-Tidal CO₂ (EtCO₂) Challenge
Tidsramme: Baseline & Change from Baseline
CVR (expressed as % BOLD signal change per mmHg EtCO₂) derived from BOLD fMRI acquired during a hypercapnic EtCO₂ challenge
Baseline & Change from Baseline
Neuroinflammation proxy as Measured by T2* relaxation times
Tidsramme: Baseline & Change from Baseline
Milliseconds (ms)
Baseline & Change from Baseline
Neuromelanin Contrast Ratio in the Substantia Nigra as Measured by Neuromelanin-Sensitive MRI
Tidsramme: Baseline & Change from Baseline
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
Baseline & Change from Baseline
Intracranial Artery Lumen Diameter as Measured by Time-of-Flight MRA
Tidsramme: Baseline & Change from Baseline
Lumen diameter (mm) measured at standardized segments of the ICA, MCA, basilar, and vertebral arteries using 3D TOF-MRA at 3T
Baseline & Change from Baseline
Body Mass Index (BMI)
Tidsramme: Baseline & Change from Baseline
BMI (kg/m²) calculated from measured height (m) and body weight (kg)
Baseline & Change from Baseline
Waist Circumference, Hip Circumference
Tidsramme: Baseline & Change from Baseline
circumference (cm)
Baseline & Change from Baseline
Waist-to-height ratio, Waist-to-hip ratio
Tidsramme: Baseline & Change from Baseline
Unitless
Baseline & Change from Baseline
Visceral Adipose Tissue as Measured by MRI
Tidsramme: Baseline & Change from Baseline
Visceral adipose tissue volume (mL) quantified by MRI Dixon sequence and Bioimpedance Analysis
Baseline & Change from Baseline
Subcutaneous Adipose Tissue as Measured by MRI
Tidsramme: Baseline & Change from Baseline
Subcutaneous adipose tissue volume (mL) quantified by MRI
Baseline & Change from Baseline
Body Composition
Tidsramme: Baseline & Change from Baseline
Whole-body fat as a percentage of total body mass (%), lean mass tissue, muscle mass measured by BIA
Baseline & Change from Baseline

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Delay Discounting Task Score (Impulsive Choice)
Tidsramme: Baseline & Change from Baseline
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.
Baseline & Change from Baseline
Penn Line Orientation Test Score (Visual Processing)
Tidsramme: Baseline & Change from Baseline
The Penn Line Orientation Test (PLOT) assesses visuospatial processing by asking participants to match line orientations. Higher scores indicate better visual processing performance.
Baseline & Change from Baseline
Penn Progressive Matrices Score (Fluid Intelligence)
Tidsramme: Baseline & Change from Baseline
The Penn Progressive Matrices is a nonverbal test of fluid reasoning and abstract problem-solving. Higher scores indicate greater fluid intelligence.
Baseline & Change from Baseline
Oral Reading Recognition Test Score (Language Ability)
Tidsramme: Baseline & Change from Baseline
The Oral Reading Recognition Test assesses language ability and reading recognition. Scores are reported as raw scores; higher scores indicate better language performance.
Baseline & Change from Baseline
Penn Word Memory Test Score (Episodic Memory)
Tidsramme: Baseline & Change from Baseline
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.
Baseline & Change from Baseline
Relational Memory Task Score (Executive Function and Attention)
Tidsramme: Baseline & Change from Baseline
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.
Baseline & Change from Baseline
Montreal Cognitive Assessment (MoCA) Total Score
Tidsramme: Baseline & Change from Baseline
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.
Baseline & Change from Baseline
Patient Health Questionnaire-9 (PHQ-9) Depression Score
Tidsramme: Baseline & Change from Baseline
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.
Baseline & Change from Baseline
Mean Daily Energy Intake, fat, carbohydrate, sugar, protein intake, saturated fatty acids intake as Assessed by 3-Day Food Record.
Tidsramme: Baseline & Change from Baseline
Daily energy intake from different macronutrients (kcal/day) derived from a 3-day food record and.
Baseline & Change from Baseline
Percentage of calories derived from each of NOVA food classification categories
Tidsramme: Baseline & Change from Baseline
Units: Percentage (%)
Baseline & Change from Baseline
Healthy Eating Index
Tidsramme: Baseline & Change from Baseline
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
Baseline & Change from Baseline
Fat Taste Preference Score
Tidsramme: Baseline & Change from Baseline
Geometric average of a preferred solution from a Monell 2-series forced choice test.
Baseline & Change from Baseline
Sweet Taste Preference Score
Tidsramme: Baseline & Change from Baseline
Geometric average of a preferred solution from a Monell 2-series forced choice test.
Baseline & Change from Baseline
Working memory capacity
Tidsramme: Baseline & Change from Baseline
Digits remembered on the digit span and digit span backwards task
Baseline & Change from Baseline
Reinforcement learning outcomes
Tidsramme: Baseline & Change from Baseline

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.
Baseline & Change from Baseline

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Alain Dagher

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Antatt)

1. august 2026

Primær fullføring (Antatt)

1. desember 2028

Studiet fullført (Antatt)

1. juni 2030

Datoer for studieregistrering

Først innsendt

3. mai 2026

Først innsendt som oppfylte QC-kriteriene

11. mai 2026

Først lagt ut (Faktiske)

18. mai 2026

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

26. juni 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

23. juni 2026

Sist bekreftet

1. juni 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • THRIVE

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

JA

IPD-planbeskrivelse

All anonymised and de-identified IPD (not biological samples) will be available to researchers on a case by case basis after trial completion.

IPD-delingstidsramme

After trial completion with no end date.

Tilgangskriterier for IPD-deling

Researchers will register to the portal and agree to terms and conditions of data use after which they will gain access to the IPD.

IPD-deling Støtteinformasjonstype

  • STUDY_PROTOCOL
  • SEVJE
  • ICF
  • ANALYTIC_CODE

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Nei

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

Abonnere