The Impact of Methadone Maintenance Therapy on Food Reward Processing in Opioid Dependence

The Impact of Methadone Maintenance Therapy on Food Intake and Food Reward Processing in Opioid Dependence: An Event-related Brain Potential Study

Methadone maintenance therapy (MMT) has shown clear efficacy for relieving opioid withdrawal symptoms and reducing the morbidity and mortality of opioid dependence. A notable phenomenon associated with MMT is increased food intake, enhanced sweet preferences, and weight gain. The underlying neural mechanisms for opioid-related overconsumption are not well understood but are thought to arise from role in 1) increasing the palatability and hedonic aspects of food and 2) diminishing satiety signaling systems. In the proposed project, the investigators will examine methadone's potential role in opioid-related overconsumption of food. The investigators propose to examine eating behavior, sucrose preferences, and an event-related potential (ERP) component that is induced by appetitive motivation for highly rewarding foods in patients with a history of opioid dependence receiving methadone maintenance therapy (O+MMT) and not receiving opioid agonist therapy (O-MMT). A matched sample of obese and overweight adults without history of opioid use (HOC) will also be examined.

Study Overview

• Status: Completed
• Conditions: Obesity; Opioid Dependence
• Intervention / Treatment: Behavioral: Sniffin' Sticks Odor Identification and Hedonic Scale; Behavioral: Sucrose Taste Preference Assessment; Behavioral: Food Preferences Task; Behavioral: Progressive Ratio (PR) Task; Procedure: Clinical Electrophysiology; Dietary supplement: Standardized Meal and Hunger and Satiety Ratings

Detailed Description

Methadone maintenance therapy (MMT) has shown clear efficacy for relieving opioid withdrawal symptoms and reducing the morbidity and mortality of opioid dependence. A notable phenomenon associated with MMT is increased food intake, enhanced sweet preferences, and weight gain. The underlying neural mechanisms for opioid-related overconsumption are not well understood but are thought to arise from role in 1) increasing the palatability and hedonic aspects of food and 2) diminishing satiety signaling systems. In the proposed project, the investigators will examine methadone's potential role in opioid-related overconsumption of food. The investigators propose to examine eating behavior, sucrose preferences, and an event-related potential (ERP) component that is induced by appetitive motivation for highly rewarding foods in patients with a history of opioid dependence receiving methadone maintenance therapy (O+MMT) and not receiving opioid agonist therapy (O-MMT). A matched sample of obese and overweight adults without history of opioid use (HOC) will also be examined. Specifically, group differences in food intake and eating behaviors in the O+MMT group relative to individuals in the O-MMT and HOC group will be examined. Individuals will complete 24-hour dietary food recalls and inventories to characterize eating behavior and food addiction. Participants will complete psychophysical measures of chemosensory functioning of sucrose preference and pleasantness and identification ratings for odors varying in participants' hedonic characteristics. Individuals will also complete validated computer tasks to assess food preferences. Differences in cortical ERPs for high-reward food relative to low-reward food and non-food items will be examined. Event-related potentials will be recorded as participants view photos of rewarding and non-rewarding food items, as well as non-food items. ERP components that index sustained attentional engagement will be measured and compared.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
    • Baltimore, Maryland, United States, 21205
      • Broadway Center for Addictions

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria:

• English-speaking individuals
• Must be between 18 and 60 years of age
• For the O+MMT group, participants must be receiving MMT for at least 3 months
• For the O-MMT group, participants must have concluded their MMT (if applicable) at least three months prior to the date of the screening visit.

Exclusion criteria:

• Individuals may not have a history of major neurological disorders
• No unstable medical issues that would affect appetite or blood glucose
• No pervasive developmental disorder or intellectual disability
• No significant visual/auditory impairment
• No history or current episode of psychosis
• No current opioid abuse
• No current antipsychotic medication use
• No major conditions that affect chemosensory function (e.g., history of nasal fracture or respiratory infection)
• Individuals with contraindication for the EEG will be excluded
• Individuals who are current pregnant or breastfeeding will not be enrolled
• For HOC, individuals with history of opioid dependence or current or past psychiatric disorders will be excluded

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Opioid dependence receiving methadone; Patients with a history of opioid dependence receiving methadone maintenance therapy will be administered Sniffin' Sticks Odor Identification and Hedonic Scale, Sucrose Taste Preference Assessment, Food Preferences Task, Progressive Ratio Task, Clinical Electrophysiology, and Standardized Meal and Hunger and Satiety Ratings	Behavioral: Sniffin' Sticks Odor Identification and Hedonic Scale; This task measures odor identification accuracy and perceived pleasantness of odors.; Behavioral: Sucrose Taste Preference Assessment; This task measures participant ratings of sucrose preference.; Behavioral: Food Preferences Task; Participants rate images of various food stimuli. Variables derived include relative preferences and reaction time (in milliseconds).; Behavioral: Progressive Ratio (PR) Task; In the PR task, the subject is required to make an increasing number of operant responses for each successive reward; Procedure: Clinical Electrophysiology; To examine motivated attention in response to food stimuli, brain electrophysiology via event related potentials (ERPs) will be assessed while participants view and rate images of food and non-food items.; Dietary supplement: Standardized Meal and Hunger and Satiety Ratings; Participants will receive a standardized meal and complete hunger and satiety ratings.
Experimental: Opioid dependence not on methadone; Patients with a history of opioid dependence not current receiving methadone maintenance therapy will be administered Sniffin' Sticks Odor Identification and Hedonic Scale, Sucrose Taste Preference Assessment, Food Preferences Task, Progressive Ratio Task, Clinical Electrophysiology, and Standardized Meal and Hunger and Satiety Ratings	Behavioral: Sniffin' Sticks Odor Identification and Hedonic Scale; This task measures odor identification accuracy and perceived pleasantness of odors.; Behavioral: Sucrose Taste Preference Assessment; This task measures participant ratings of sucrose preference.; Behavioral: Food Preferences Task; Participants rate images of various food stimuli. Variables derived include relative preferences and reaction time (in milliseconds).; Behavioral: Progressive Ratio (PR) Task; In the PR task, the subject is required to make an increasing number of operant responses for each successive reward; Procedure: Clinical Electrophysiology; To examine motivated attention in response to food stimuli, brain electrophysiology via event related potentials (ERPs) will be assessed while participants view and rate images of food and non-food items.; Dietary supplement: Standardized Meal and Hunger and Satiety Ratings; Participants will receive a standardized meal and complete hunger and satiety ratings.
Active Comparator: Healthy controls; Healthy controls without history of opioid use will be administered Sniffin' Sticks Odor Identification and Hedonic Scale, Sucrose Taste Preference Assessment, Food Preferences Task, Progressive Ratio Task, Clinical Electrophysiology, and Standardized Meal and Hunger and Satiety Ratings	Behavioral: Sniffin' Sticks Odor Identification and Hedonic Scale; This task measures odor identification accuracy and perceived pleasantness of odors.; Behavioral: Sucrose Taste Preference Assessment; This task measures participant ratings of sucrose preference.; Behavioral: Food Preferences Task; Participants rate images of various food stimuli. Variables derived include relative preferences and reaction time (in milliseconds).; Behavioral: Progressive Ratio (PR) Task; In the PR task, the subject is required to make an increasing number of operant responses for each successive reward; Procedure: Clinical Electrophysiology; To examine motivated attention in response to food stimuli, brain electrophysiology via event related potentials (ERPs) will be assessed while participants view and rate images of food and non-food items.; Dietary supplement: Standardized Meal and Hunger and Satiety Ratings; Participants will receive a standardized meal and complete hunger and satiety ratings.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-related potentials measured via BrainVision actiCHamp system	Cortical ERPs for high-reward food relative to low-reward food and non-food items will be measured using a BrainVision actiCHamp system (32-channel amplifier). For each group, the grand averages and standard deviations for the late positive potential will be calculated. Group differences in LPP will be assessed within and between picture categories for each arm of the study.	At baseline visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chemosensory Processing	For the odorants, participants provide a rating of intensity and pleasantness based on a -5 to 5 point scale for each of the 16 markers. Afterwards, averages of all 16 marker scores will be calculated for the mean ratings of intensity and pleasantness. Odor identification accuracy will be assessed for each marker, with the score representing the total items correct out of 16.	At baseline visit
Food Preferences Task	Participants are showed images of high fat savory, low fat savory, high fat sweet, and low fat sweet foods. Participants must select one of the two pictures to answer the question "which food item do you most want to eat right now." Selection averages of each category and time for selection, for each arm of the study, are automatically calculated by E-Prime software.	At baseline visit
Progressive Ratio Task	Participants begin with 20 M&Ms and a computer prompt that specifies how many times the mouse must be clicked to earn a piece of candy. Participants can earn as little as desired. The click ratio starts at 10 and geometrically increases in increments of 2 (i.e., 10, 20, 40, 80, etc.). The computer program E-Prime automatically records the participant's work capacity and the administrator records the number of M&Ms left in the cup.	At baseline visit

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Mid-Atlantic Nutrition Obesity Research Center
• Investigators: Principal Investigator: Vidya Kamath, Ph.D., Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2018
• Primary Completion (Actual): December 1, 2019
• Study Completion (Actual): June 1, 2020

Study Registration Dates

• First Submitted: June 21, 2018
• First Submitted That Met QC Criteria: June 29, 2018
• First Posted (Actual): July 2, 2018

Study Record Updates

• Last Update Posted (Actual): December 16, 2020
• Last Update Submitted That Met QC Criteria: December 14, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: obesity; opioid dependence; methadone; food reward; olfactory
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Opioid-Related Disorders
• Other Study ID Numbers: IRB00092798; P30DK072488 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No