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Effect of mCPP on Cognitive Control, Appetite, and Neural Responses (mCPP)

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ClinicalTrials.gov Identifier: NCT03962829
Recruitment Status : Recruiting
First Posted : May 24, 2019
Last Update Posted : May 29, 2019
Sponsor:
Collaborator:
University Hospital Birmingham
Information provided by (Responsible Party):
University of Birmingham

Tracking Information
First Submitted Date  ICMJE May 22, 2019
First Posted Date  ICMJE May 24, 2019
Last Update Posted Date May 29, 2019
Actual Study Start Date  ICMJE February 1, 2019
Estimated Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 22, 2019)
fMRI brain response during food reward processes [ Time Frame: 21 min ]
Brain responses for food stimuli compared to non-food stimuli. The researchers will measure this by showing subjects food and non-food images while preforming and fMRI-scan and subtract activity during non-food images from the activity pattern when looking at food images.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03962829 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 22, 2019)
  • fMRI brain response during inhibition processes [ Time Frame: 20 min ]
    Neural activation during delay discounting paradigm for both food and monetary reward choices
  • Emotional categorisation [ Time Frame: 10 min ]
    Accuracy of category and reaction time will be measured for dislike or like words
  • Emotional recall part 1 [ Time Frame: 4 min ]
    Recall words of liked and disliked words will be recorded in ECAT
  • Emotional recall part 1 [ Time Frame: 10 min ]
    Accuracy of previous exposed or not exposed words will be measured
  • Pasta intake [ Time Frame: 20 min ]
    Amount (kcal and gram) of pasta eaten will be measured
  • Cookies intake [ Time Frame: 10 min ]
    Amount (kcal and gram) of cookies eaten will be measured
  • fMRI neural network [ Time Frame: 10 min ]
    Functional connectivity during resting state
  • VPA [ Time Frame: 20 min ]
    Verbal pair association tasks, correct amount of word pairs remembered
  • N-back [ Time Frame: 10 min ]
    N-back tasks, measure of working memory and working memory capacity
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of mCPP on Cognitive Control, Appetite, and Neural Responses
Official Title  ICMJE The Effect of Oral Administration of Meta-chlorophenylpiperazine (mCPP) on Cognitive Processes, Appetite, and Related Neural Responses in Healthy Lean and Obese Participants
Brief Summary

Previous studies have reported that the 5-HT2C receptor agonist meta-chlorophenylpiperazine (mCPP) decreases appetite and food intake in humans1-3. 5-HT2C receptor activation inhibits dopamine and norepinephrine release in the brain4, and has also been linked to diabetes5. The specificity of the effect of mCPP on human appetite is unclear, as previous studies also reported an increase in nausea1,3. The drug has also been reported to increase anxiety and cause panic attacks when given in a bolus dose intravenously6. Previous findings in our laboratory showed that mCPP reduced appetite, increased satiety in women and enhanced memory in the P1vital® Oxford Emotional Test Battery3. Following up on these results a food intake and fMRI study was performed, in which it was observed that mCPP decreased intake of a palatable snack (hedonic eating) and dlPFC and insula BOLD responses to food pictures. Additionally it increased memory and food value responses in brain after mCPP administration (Thomas et al submitted).

It is well established that eating behaviour is affected by metabolic signals (e.g. insulin, ghrelin, serotonin) and is also modulated via food reward processes7. More recently it has been proposed that eating is also modulated via higher cognitive processes such as inhibitory control, attention, and memory. However, in humans, eating behaviour seems to be a more complex process, which involves habits, long-term goals and social interaction. Thus, cognitive processes appear to play an important role in food consumption. In the proposed study the researchers investigate the effect of administering mCPP, on eating, and on metabolic, reward and cognitive processes and the potential interplay between these functions.

Detailed Description

The prevalence of overweight and obesity has increased rapidly in less than half a century. It is assumed that this development is due to interplay between behavioural, environmental and genetic factors. This increase in weight is associated with multiple-medical conditions, e.g. increased depression, and chronicle health conditions, like heart disease, cancer, and type 2 diabetes, and is associated with high health care costs. The UK has one of the highest rates of obesity in Europe, with 20% of the population defined as obese and over 50% defined as overweight. However treatment options for weight loss, and especially long-term weight maintenance are still limited. The development of safe and effective therapeutics is therefore imperative. An effective way to help weight loss, as part of a comprehensive program, is to prescribe drug treatments designed to reduce food consumption. However, at present, drug treatments for obesity are very limited.

mCPP appears to reduce food intake, and appetite in lean people. However it also seems to effect cognitive processes. Basic research to understand the interplay between these processes in relation to drug effects on appetite are of great interest because it can provide important insight into new development novel treatments for obesity. The investigators propose to test a model outlining that metabolic signals may reduce food intake by interfering with cognitive processes that underpin appetite.

It has been agreed upon that eating behaviour is affected by metabolic signals, e.g. serotonin, insulin and ghrelin, and influenced by food reward processes (Berthoud 2011). But the idea that these mechanisms are modulated via higher cognitive processes such as inhibitory control, attention, and memory is a relatively new domain to be explored. In humans, eating behaviour seems to be a more complex system; which also involves habits, long-term goals, and social interaction. Cognitive processes appear to play an important role in food consumption. Previous studies reported the anorectic effect of the drugs meta-chloriphenylpiperazine (mCPP), a 5-HT2C receptor agonist. Additionally mCPP has been shown to reduce appetite, increase satiety, and enhance memory for emotional material (word recall) and recognition memory (Thomas et al 2015). Preliminary results suggest that mCPP decreased intake of palatable snacks (hedonic eating) and when viewing food pictures appetite and reward related neural responses appear to be modulated by mCPP administration (Thomas et al in preparation). However the interaction between the drugs, neural responses and behaviour are still not known, and the effects of overweight on these responses is a very interesting question in relation to anti-obesity drug development.

In the proposed study the researchers want to investigate the effect of oral administrating mCPP, on neural responses and networks in relation to food reward, cognitive control and working memory and its impact on subsequent snack consumption, food and emotion related memory, and mood and appetite ratings, and additionally the interplay between all these processes in both lean and obese individuals. Participants will get an mCPP dose (30mg) and a placebo on different occasion, where after the neural activation (with fMRI) in response to food stimuli is assesed, inhibition tasks, and memory tests. This will be related to eating behaviour, memory performance, and mood and appetite ratings.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:
counter-balanced, double-blind, placebo-controlled, crossover, within-subject design
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:
The research will be double blind; both placebo and mCPP will be presented in an identical capsule, therefore the participants and researchers do not know which treatment the participants will receive. A qualified pharmacist will follow standard operating procedures to encase the pharmacy prepared medications in a gelatine capsule in order to match the size and the appearance of the placebo. An independent researcher will prepare counterbalanced randomisation in advance.
Primary Purpose: Basic Science
Condition  ICMJE
  • Eating Behavior
  • Obesity
Intervention  ICMJE
  • Drug: mCPP
    Healthy participants administrate one capsule of mCPP (30mg)
    Other Name: meta-chlorophenylpiperazine
  • Drug: Placebo oral tablet
    Healthy participants administrate one capsule of placebo (containing lactose)
Study Arms  ICMJE
  • Placebo Comparator: Placebo condition
    Participants receive placebo capsule
    Intervention: Drug: Placebo oral tablet
  • Active Comparator: mCPP condition
    Participants receive active (mCPP) capsule
    Intervention: Drug: mCPP
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 22, 2019)
80
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2019
Estimated Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Healthy female subjects
  • Age 18-65 years at start of the study
  • Body Mass Index (BMI) between 18 and 25 kg/m2 for the lean group and between 30 and 40 kg/m2 for the obese group
  • Right-handedness (including left-handers could bias the results because of the laterality of brain functions)
  • Ability to give informed consent
  • Fluent English speaking
  • Willingness to be informed about chance findings of pathology

Exclusion Criteria:

  • Subjects who have a non-removable metal object in or at their body, such as, for example: Heart pace-maker, artificial heart valve, metal prosthesis, implants or splinters, non-removable dental braces
  • Tattoos, that are older than 15 years
  • Claustrophobia
  • Limited temperature perception and/or increased sensitivity to warming of the body
  • Pathological hearing ability or an increased sensitivity to loud noises
  • Lack of ability to give informed consent
  • Operation less than three months ago
  • Simultaneous participation in other studies that involve drugs intake or blood spending
  • Acute illness or infection during the last 4 weeks
  • Cardiovascular disorders (e.g., hypertrophic cardiomyopathy, long QT syndrome)
  • Moderate or severe head injury
  • Eating disorders
  • No metabolic (e.g. metabolic disorder, diabetes, insulin resistance), psychological (e.g. depression) or neurological (e.g. epilepsy, headache disorder, multiple sclerosis, traumatic brain injuries) diseases or medication in relation to these diseases.
  • Intake of any medication that can interfere with the drug or measurements.
  • Current weight loss regimens, or more then 5kg weight loss in the last 3 months
  • Smoking
  • Current pregnancy or breastfeeding
  • Current or past history of drug or alcohol dependency - alcohol consumption exceeding 12 units a week
  • Food allergies (e.g. peanut allergy lactose and gluten intolerance) or vegetarian/vegan diet
  • Disliking the study lunch
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Gender Based Eligibility: Yes
Gender Eligibility Description: We aim to recruit 50% male and 50% female particpants
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Maartje Spetter, PhD +44 (0) 121 41 ext 42865 m.s.spetter@bham.a.cuk
Contact: Suzanne Higgs, PhD +44 (0) 121 41 ext 44907 S.Higgs.1@bham.ac.uk
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03962829
Other Study ID Numbers  ICMJE RG_16_214
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: The study protocol and data will be shared on Open Science Forum
Supporting Materials: Study Protocol
Time Frame: The study protocol and data will become available after the last participant has finished the study.
Access Criteria: All researchers
URL: https://osf.io
Responsible Party University of Birmingham
Study Sponsor  ICMJE University of Birmingham
Collaborators  ICMJE University Hospital Birmingham
Investigators  ICMJE
Principal Investigator: Maartje Spetter, PhD University fo Birmingham
PRS Account University of Birmingham
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP