Opening soonPhase 4Interventional
What this study is about
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
A promising-looking record is not the same as confirmed eligibility. The study team must review the full criteria and current recruitment status.
Basic eligibility
Age35 Years to 55 Years
SexAll
Healthy volunteersAccepted
ConditionClass I/II Obesity
Full registry 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.
Primary outcomes
Serum C-reactive Protein (CRP)Baseline & Change from BaselineFasting serum CRP concentration (mg/L)
Serum Pro-inflammatory Cytokines (Interleukin-6, TNF-α, Interleukin-1β, and IL-1 Receptor Antagonist)Baseline & Change from BaselineFasting serum concentrations of IL-6, TNF-α, IL-1β, and IL-1 receptor antagonist (all in pg/mL)
Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)Baseline & Change from BaselineHOMA-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.
Fasting Plasma GlucoseBaseline & Change from BaselineVenous plasma glucose concentration (mmol/L) following an overnight fast
Glycated Hemoglobin A1c (HbA1c)Baseline & Change from BaselinePercentage of glycated hemoglobin (%), reflecting mean blood glucose
Serum LeptinBaseline & Change from BaselineFasting serum leptin concentration (ng/mL)
Serum GhrelinBaseline & Change from BaselineFasting serum ghrelin concentration (pg/mL)
Serum AdiponectinBaseline & Change from BaselineFasting serum adiponectin concentration (μg/mL)
