Translational Health Research Into Vascular and Neurocognitive Effects of Weight Loss
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: semaglutide.
- Who it may be relevant to
- Registry conditions: Class I/II Obesity. Basic parameters: 35 years — 55 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Canada
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
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
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.
Interventions
- Drug 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.
Primary outcome measures
- Serum C-reactive Protein (CRP) [Time frame: Baseline & Change from Baseline]
- Serum Pro-inflammatory Cytokines (Interleukin-6, TNF-α, Interleukin-1β, and IL-1 Receptor Antagonist) [Time frame: Baseline & Change from Baseline]
- Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) [Time frame: Baseline & Change from Baseline]
- Fasting Plasma Glucose [Time frame: Baseline & Change from Baseline]
- Glycated Hemoglobin A1c (HbA1c) [Time frame: Baseline & Change from Baseline]
- Serum Leptin [Time frame: Baseline & Change from Baseline]
- Serum Ghrelin [Time frame: Baseline & Change from Baseline]
- Serum Adiponectin [Time frame: Baseline & Change from Baseline]
- Fasting Serum Insulin [Time frame: Baseline & Change from Baseline]
- Serum Glucagon-Like Peptide-1 (GLP-1) [Time frame: Baseline & Change from Baseline]
Secondary outcome measures (12)
- Delay Discounting Task Score (Impulsive Choice) [Time frame: Baseline & Change from Baseline]
- Penn Line Orientation Test Score (Visual Processing) [Time frame: Baseline & Change from Baseline]
- Penn Progressive Matrices Score (Fluid Intelligence) [Time frame: Baseline & Change from Baseline]
- Oral Reading Recognition Test Score (Language Ability) [Time frame: Baseline & Change from Baseline]
- Penn Word Memory Test Score (Episodic Memory) [Time frame: Baseline & Change from Baseline]
- Relational Memory Task Score (Executive Function and Attention) [Time frame: Baseline & Change from Baseline]
- Montreal Cognitive Assessment (MoCA) Total Score [Time frame: Baseline & Change from Baseline]
- Patient Health Questionnaire-9 (PHQ-9) Depression Score [Time frame: Baseline & Change from Baseline]
- 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]
- Percentage of calories derived from each of NOVA food classification categories [Time frame: Baseline & Change from Baseline]
- Healthy Eating Index [Time frame: Baseline & Change from Baseline]
- Fat Taste Preference Score [Time frame: Baseline & Change from Baseline]
Eligibility criteria
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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Allocation
- Non-randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
Canada · 1 center
- The Montreal Neurological Institute-Hospital — Montreal
Identifiers
NCT: NCT07592546 · THRIVE