The Effects of Methylphenidate on the Reduction of Food Energy Intake and on the Augmentation of Energy Expenditure
试验速览
- 阶段
- 3 期
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Change in Energy Intake
研究概览
简要总结
The Problem: Obesity is one of the leading causes of chronic disease and death. The efficacy of diet and exercise to sustain weight loss over the long term is weak. While pharmacotherapy is more effective than behavior intervention in maintaining weight loss the effects are often not sufficient to achieve optimal health benefits. Current drug treatments may be sub-optimal because they do not directly target the rewarding value of food, drive to eat, food liking, and impulsivity for eating energy dense snack foods, all of which influences both quantity and quality of food intake and impacts adherence needed to maintain weight loss.
The Solution: The limitations in current anti-obesity agents are potentially addressed by Methylphenidate (MPH). We showed that MPH reduces food intake, dietary fat intake, hunger and food reward, as increase resting energy expenditure in obese and non-obese adults;however, no controlled field trials have been conducted in obese individuals without ADHD.
Objectives/Hypotheses: Primary: To test the effects of MPH on energy intake in obese men and women. Secondary: to examine the effects of MPH on energy expenditure, body weight, impulsivity, food reward, and olfaction. The investigators predict that compared to placebo, MPH will show reduced appetite, along with reduced impulsivity, food reward, and smell function.
Deliverable: This study may be the first to establish the short-term efficacy and safety of using MPH for weight loss, and if successful, data will inform a larger trial that can potentially identify MPH as a novel therapeutic agent for treating obesity and related chronic diseases in a predisposed population.
详细描述
Research Objectives and Hypotheses
Primary: The primary objective of this study is to examine whether Methylphenidate (MPH) at dose of 0.50 mg/kg (not exceeding 100 mg/day) can lead to a sustained reduction in energy intake in obese adolescents and adults. Based on the investigators' pilot data in adults, it is predicted that daily administration of MPH for 60 consecutive days will produce reductions in food intake (both in lab and free-living) compared to placebo, extending our previous findings to a longer period of time and to obese adolescents. Prior to beginning the intervention, both MPH and placebo treatment groups will receive lifestyle advice (eating and exercise guidelines for healthy living). The primary outcome measures will rely on the validated measurements of energy intake (in lab lunch buffet and out of lab 3 day food menu).
Secondary objectives/hypotheses: The effects of MPH on all components of energy expenditure will be investigated. Based on the investigators' pilot data, it is predicted that from Baseline to 60 days, MPH will increase total energy expenditure (TEE) when compared with placebo, mostly through greater resting energy expenditure (REE) and thermic effects of food (TEF). It is hypothesized that after the 60-day intervention the MPH group will experience a significantly attenuated reduction in REE compared to placebo. We predict that the MPH group will lose body weight at 2 months, whereas, it is predicted that there will be no change in body weight for the placebo. The investigators will also explore the effects of MPH on macronutrient preference and consumption, and on the rewarding value of energy dense snack foods. Based on previous findings, the investigators predict that MPH will reduce consumption of energy dense, high fat/sugar foods but have little effect on consumption of foods low in calories, fats or sugars. In addition, it is predicted that the reduction in intake of energy dense, high fat/sugar foods will be mediated by reductions in the rewarding value of food and impulsivity as measured by well validated computerized simulations. Also explored will be the effects of MPH on olfaction and it is predicted that compared to placebo, individuals taking MPH will have reduced smell function. It is also predicted the MPH group will show reduced appetite sensations, reduced rewarding value of food, reduced impulsivity for snack food, and reduced palatability ratings of food compared to placebo at 2 months.
Trial Design
The trial design will consist of a randomized, double blind, placebo-controlled 2 parallel arm study. The two randomly assigned treatment groups will consist of administrating a placebo or short-acting MPH two-times daily 1 hour before meals for a period of 2 months (60 consecutive days). Prior to being randomized into either the placebo group or the experimental (MPH) group, subjects will first have had to respond to a recruitment poster, newspaper advertisement. Once it is determined with that initial screening that the participant still meets inclusion criteria, they will be invited to come to the laboratory for a screening visit to determine whether they meet eligibility criteria, to sign informed consent, and to take a test dose of MPH in order for a nurse to closely monitor any potential side-effects prior to starting the 2-times daily dosing of MPH or placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 16 Years 至 40 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •males and females 16 to 40 years old
- •BMI in the obese category (above 29.9kg/m2)
- •willing to comply with procedures, and sign informed consent forms
- •able to swallow a placebo pill that will be used in the study (same size as study drug)
排除标准
- •smoker (the main outcome is energy intake and smoking is known to impact appetite)
- •known serious food allergies, including lactose
- •history of previous MPH use or allergy to MPH
- •history of ADHD or current diagnosis of an axis 1 psychiatric disorder (e.g., depression, panic disorder, schizophrenia) as measured by self-report, the Wender-Utah Rating Scale52-54 and the Beck Depression Inventory
- •current use of antidepressants, thyroid medication, or any medication that could affect appetite
- •high blood pressure
- •pre-existing cardiovascular disorders including uncontrolled hypertension, angina pectoris, arterial occlusive disease, heart failure, cardiomypathies, myocardial infarction, and cardiac arrhythmia
- •excessive use of alcohol or alcoholism, or current addictions to opiates, cocaine or stimulants as measured by the Drug Abuse Screening Test;
- •not a restrained eater based on cut-score (11 or higher) on Three Factor Eating Questionnaire56
- •personal or family history of seizure disorders
- •currently taking MAO inhibitors, pressor agents, coumarin, anticonvulsants, phenylbutazone, or tricyclic antidepressants
- •history of thyroid disease
- •personal or family history of motor tics or Tourettes's Syndrome
- •not pregnant, as determined by commercially available pregnancy test taken by female participants prior to test dose of MPH.
- •after the test dose of MPH, systolic blood pressure exceeding baseline reading by 20mmHg, diastolic blood pressure exceeding the baseline reading by 10mmHg, BP > 160/100, or resting pulse increased by 20 beats/minute from the baseline.
研究组 & 干预措施
Placebo
60 day oral administration of sugar placebo twice per day before lunch and supper.
干预措施: Placebo (Drug)
Methylphenidate (MPH)
60 day oral administration of active study drug (methylphenidate) twice per day before lunch and supper.
干预措施: MPH (Drug)
结局指标
主要结局
Change in Energy Intake
时间窗: Measured three times over the course of 2 months (twice at baseline: once with and without study drug & once at final visit).
Participant will be offered a lunch buffet that includes items they indicate are preferred. They will be able to eat as much or as little as they choose.
次要结局
- Change in Energy Expenditure(Measured three times over the course of 2 months (twice at baseline: once with and without study drug & once at final visit).)
- Change in Body Weight(Measured two times over the course of 2 months (once at baseline & once at final visit).)
- Height(Measured at final visit; height will be used to determine BMI at the final visit.)
- Change in Body Mass Index(Measured two times over the course of 2 months (once at baseline & once at final visit).)
- Change in Impulsivity towards food and non-food reward as measured by reaction time on a computer task.(Measured three times over the course of 2 months (twice at baseline: once with and without study drug & once at final visit).)
- Change in Odour Detection Threshold measured with Sniffin' Sticks Odourized Pens(Measured three times over the course of 2 months (twice at baseline: once with and without study drug & once at final visit).)
研究者
Phillippe Robaey
Qualified Investigator, MD, PhD, FRCPC
Children's Hospital of Eastern Ontario