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

tiistai 23. kesäkuuta 2026 päivittänyt: 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

Tutkimuksen yleiskatsaus

Tila

Ei vielä rekrytointia

Ehdot

Interventio / Hoito

Yksityiskohtainen kuvaus

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.

Opintotyyppi

Interventio

Ilmoittautuminen (Arvioitu)

240

Vaihe

  • Vaihe 4

Yhteystiedot ja paikat

Tässä osiossa on tutkimuksen suorittajien yhteystiedot ja tiedot siitä, missä tämä tutkimus suoritetaan.

Opiskeluyhteys

Tutki yhteystietojen varmuuskopiointi

Opiskelupaikat

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

Osallistumiskriteerit

Tutkijat etsivät ihmisiä, jotka sopivat tiettyyn kuvaukseen, jota kutsutaan kelpoisuuskriteereiksi. Joitakin esimerkkejä näistä kriteereistä ovat henkilön yleinen terveydentila tai aiemmat hoidot.

Kelpoisuusvaatimukset

Opintokelpoiset iät

  • Aikuinen

Hyväksyy terveitä vapaaehtoisia

Joo

Kuvaus

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.

Opintosuunnitelma

Tässä osiossa on tietoja tutkimussuunnitelmasta, mukaan lukien kuinka tutkimus on suunniteltu ja mitä tutkimuksella mitataan.

Miten tutkimus on suunniteltu?

Suunnittelun yksityiskohdat

  • Ensisijainen käyttötarkoitus: Hoito
  • Jako: Ei satunnaistettu
  • Inventiomalli: Rinnakkaistehtävä
  • Naamiointi: Ei mitään (avoin tarra)

Aseet ja interventiot

Osallistujaryhmä / Arm
Interventio / Hoito
Kokeellinen: Overweight Group (BMI 27 - 40 kg/m2)
semaglutide
Lääke: 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.
Muut nimet:
  • Ozempic
  • Wegovy
Ei väliintuloa: Lean group (BMI 20 - 25 kg/m2)

Mitä tutkimuksessa mitataan?

Ensisijaiset tulostoimenpiteet

Tulosmittaus
Toimenpiteen kuvaus
Aikaikkuna
Serum C-reactive Protein (CRP)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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
Aikaikkuna: Baseline & Change from Baseline
Venous plasma glucose concentration (mmol/L) following an overnight fast
Baseline & Change from Baseline
Glycated Hemoglobin A1c (HbA1c)
Aikaikkuna: Baseline & Change from Baseline
Percentage of glycated hemoglobin (%), reflecting mean blood glucose
Baseline & Change from Baseline
Serum Leptin
Aikaikkuna: Baseline & Change from Baseline
Fasting serum leptin concentration (ng/mL)
Baseline & Change from Baseline
Serum Ghrelin
Aikaikkuna: Baseline & Change from Baseline
Fasting serum ghrelin concentration (pg/mL)
Baseline & Change from Baseline
Serum Adiponectin
Aikaikkuna: Baseline & Change from Baseline
Fasting serum adiponectin concentration (μg/mL)
Baseline & Change from Baseline
Fasting Serum Insulin
Aikaikkuna: Baseline & Change from Baseline
Fasting serum insulin concentration (μIU/mL)
Baseline & Change from Baseline
Serum Glucagon-Like Peptide-1 (GLP-1)
Aikaikkuna: Baseline & Change from Baseline
Serum total GLP-1 concentration (pmol/L)
Baseline & Change from Baseline
Serum C-peptide
Aikaikkuna: 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])
Aikaikkuna: 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)
Aikaikkuna: Baseline & Change from Baseline
Fasting serum ApoB concentration (g/L)
Baseline & Change from Baseline
Red Blood Cell Phospholipid Fatty Acid Composition
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: Baseline & Change from Baseline
Mean cortical thickness (mm) derived from T1-weighted
Baseline & Change from Baseline
Grey Matter Volume as Measured by Structural MRI
Aikaikkuna: 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
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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])
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: Baseline & Change from Baseline
Milliseconds (ms)
Baseline & Change from Baseline
Neuromelanin Contrast Ratio in the Substantia Nigra as Measured by Neuromelanin-Sensitive MRI
Aikaikkuna: 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
Aikaikkuna: 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)
Aikaikkuna: Baseline & Change from Baseline
BMI (kg/m²) calculated from measured height (m) and body weight (kg)
Baseline & Change from Baseline
Waist Circumference, Hip Circumference
Aikaikkuna: Baseline & Change from Baseline
circumference (cm)
Baseline & Change from Baseline
Waist-to-height ratio, Waist-to-hip ratio
Aikaikkuna: Baseline & Change from Baseline
Unitless
Baseline & Change from Baseline
Visceral Adipose Tissue as Measured by MRI
Aikaikkuna: 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
Aikaikkuna: Baseline & Change from Baseline
Subcutaneous adipose tissue volume (mL) quantified by MRI
Baseline & Change from Baseline
Body Composition
Aikaikkuna: 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

Toissijaiset tulostoimenpiteet

Tulosmittaus
Toimenpiteen kuvaus
Aikaikkuna
Delay Discounting Task Score (Impulsive Choice)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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.
Aikaikkuna: 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
Aikaikkuna: Baseline & Change from Baseline
Units: Percentage (%)
Baseline & Change from Baseline
Healthy Eating Index
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: Baseline & Change from Baseline
Digits remembered on the digit span and digit span backwards task
Baseline & Change from Baseline
Reinforcement learning outcomes
Aikaikkuna: 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

Yhteistyökumppanit ja tutkijat

Täältä löydät tähän tutkimukseen osallistuvat ihmiset ja organisaatiot.

Sponsori

Alain Dagher

Opintojen ennätyspäivät

Nämä päivämäärät seuraavat ClinicalTrials.gov-sivustolle lähetettyjen tutkimustietueiden ja yhteenvetojen edistymistä. National Library of Medicine (NLM) tarkistaa tutkimustiedot ja raportoidut tulokset varmistaakseen, että ne täyttävät tietyt laadunvalvontastandardit, ennen kuin ne julkaistaan ​​julkisella verkkosivustolla.

Opi tärkeimmät päivämäärät

Opiskelun aloitus (Arvioitu)

Lauantai 1. elokuuta 2026

Ensisijainen valmistuminen (Arvioitu)

Perjantai 1. joulukuuta 2028

Opintojen valmistuminen (Arvioitu)

Lauantai 1. kesäkuuta 2030

Opintoihin ilmoittautumispäivät

Ensimmäinen lähetetty

Sunnuntai 3. toukokuuta 2026

Ensimmäinen toimitettu, joka täytti QC-kriteerit

Maanantai 11. toukokuuta 2026

Ensimmäinen Lähetetty (Todellinen)

Maanantai 18. toukokuuta 2026

Tutkimustietojen päivitykset

Viimeisin päivitys julkaistu (Todellinen)

Perjantai 26. kesäkuuta 2026

Viimeisin lähetetty päivitys, joka täytti QC-kriteerit

Tiistai 23. kesäkuuta 2026

Viimeksi vahvistettu

Maanantai 1. kesäkuuta 2026

Lisää tietoa

Tähän tutkimukseen liittyvät termit

Avainsanat

Muita asiaankuuluvia MeSH-ehtoja

Muut tutkimustunnusnumerot

  • THRIVE

Yksittäisten osallistujien tietojen suunnitelma (IPD)

Aiotko jakaa yksittäisten osallistujien tietoja (IPD)?

JOO

IPD-suunnitelman kuvaus

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

IPD-jaon aikakehys

After trial completion with no end date.

IPD-jaon käyttöoikeuskriteerit

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-jakamista tukeva tietotyyppi

  • STUDY_PROTOCOL
  • MAHLA
  • ICF
  • ANALYTIC_CODE

Lääke- ja laitetiedot, tutkimusasiakirjat

Tutkii yhdysvaltalaista FDA sääntelemää lääkevalmistetta

Ei

Tutkii yhdysvaltalaista FDA sääntelemää laitetuotetta

Ei

Nämä tiedot haettiin suoraan verkkosivustolta clinicaltrials.gov ilman muutoksia. Jos sinulla on pyyntöjä muuttaa, poistaa tai päivittää tutkimustietojasi, ota yhteyttä register@clinicaltrials.gov. Heti kun muutos on otettu käyttöön osoitteessa clinicaltrials.gov, se päivitetään automaattisesti myös verkkosivustollemme .

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