Translational Health Research Into Vascular and Neurocognitive Effects of Weight Loss
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 240
- 试验地点
- 1
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 35 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Overweight Group (BMI 27 - 40 kg/m2)
semaglutide
干预措施: semaglutide (Drug)
Lean group (BMI 20 - 25 kg/m2)
结局指标
主要结局
未指定
次要结局
- Working memory capacity(Baseline & Change from Baseline)
- Reinforcement learning outcomes(Baseline & Change from Baseline)
研究者
Alain Dagher
Principal Investigator
McGill University