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

23 czerwca 2026 zaktualizowane przez: 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

Przegląd badań

Status

Jeszcze nie rekrutacja

Warunki

Interwencja / Leczenie

Szczegółowy opis

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.

Typ studiów

Interwencyjne

Zapisy (Szacowany)

240

Faza

  • Faza 4

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Kontakt w sprawie studiów

Kopia zapasowa kontaktu do badania

Lokalizacje studiów

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

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

  • Dorosły

Akceptuje zdrowych ochotników

Tak

Opis

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.

Plan studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Leczenie
  • Przydział: Nielosowe
  • Model interwencyjny: Przydział równoległy
  • Maskowanie: Brak (otwarta etykieta)

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Eksperymentalny: Overweight Group (BMI 27 - 40 kg/m2)
semaglutide
Lek: 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.
Inne nazwy:
  • Ozempic
  • Węgowy
Brak interwencji: Lean group (BMI 20 - 25 kg/m2)

Co mierzy badanie?

Podstawowe miary wyniku

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

Miary wyników drugorzędnych

Miara wyniku
Opis środka
Ramy czasowe
Delay Discounting Task Score (Impulsive Choice)
Ramy czasowe: 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)
Ramy czasowe: 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)
Ramy czasowe: 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)
Ramy czasowe: 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)
Ramy czasowe: 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)
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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.
Ramy czasowe: 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
Ramy czasowe: Baseline & Change from Baseline
Units: Percentage (%)
Baseline & Change from Baseline
Healthy Eating Index
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: Baseline & Change from Baseline
Digits remembered on the digit span and digit span backwards task
Baseline & Change from Baseline
Reinforcement learning outcomes
Ramy czasowe: 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

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

Alain Dagher

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów (Szacowany)

1 sierpnia 2026

Zakończenie podstawowe (Szacowany)

1 grudnia 2028

Ukończenie studiów (Szacowany)

1 czerwca 2030

Daty rejestracji na studia

Pierwszy przesłany

3 maja 2026

Pierwszy przesłany, który spełnia kryteria kontroli jakości

11 maja 2026

Pierwszy wysłany (Rzeczywisty)

18 maja 2026

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Rzeczywisty)

26 czerwca 2026

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

23 czerwca 2026

Ostatnia weryfikacja

1 czerwca 2026

Więcej informacji

Terminy związane z tym badaniem

Słowa kluczowe

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

  • THRIVE

Plan dla danych uczestnika indywidualnego (IPD)

Planujesz udostępniać dane poszczególnych uczestników (IPD)?

TAK

Opis planu IPD

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

Ramy czasowe udostępniania IPD

After trial completion with no end date.

Kryteria dostępu do udostępniania IPD

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

Typ informacji pomocniczych dotyczących udostępniania IPD

  • PROTOKÓŁ BADANIA
  • SOK ROŚLINNY
  • ICF
  • ANALITYCZNY_KOD

Informacje o lekach i urządzeniach, dokumenty badawcze

Bada produkt leczniczy regulowany przez amerykańską FDA

Nie

Bada produkt urządzenia regulowany przez amerykańską FDA

Nie

Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .

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