Targeting Drug Memories With Methylphenidate

• ClinicalTrials.gov Identifier: NCT05978167
• Recruitment Status: Recruiting
• First Posted: August 7, 2023
• Last Update Posted: August 7, 2023
• Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborator: National Institute on Drug Abuse (NIDA)
• Information provided by (Responsible Party): Rita Goldstein, Icahn School of Medicine at Mount Sinai

Study Description

Brief Summary:

This study aims to identify the neural, behavioral, and pharmacological mechanisms promoting diminished expression of drug-related memories in human drug addiction. In this fMRI study with a within-subjects placebo-controlled double-blind cross-over design, oral methylphenidate (20 mg) or placebo will be administered to individuals with cocaine use disorders (CUD) to peak during the retrieval of a drug-cue memory before extinction; in addition to fMRI activations, skin conductance responses (SCR, acquired simultaneously) will serve as the psychophysiological indicators of memory modification. Assessments of interference with the return of drug-cue memories via SCR and craving will be conducted the day following MRI. This pharmocologically-enhanced behavioral approach to decreasing drug memories and craving in iCUD could ultimately be used to develop effective cue-exposure therapies for drug addiction. Procedures include MRI, blood draw, questionnaires and interviews, skin conductance response measures, and behavioral tasks.

Condition or disease	Intervention/treatment	Phase
Substance Use Disorder; Cocaine Use Disorder	Drug: Methylphenidate; Behavioral: Memory reconsolidation; Drug: Placebo	Early Phase 1

Detailed Description:

Cue-exposure therapy has not proven efficacious in reducing relapse in drug addiction, illuminating the need for alternative strategies. Here researchers will test the neural correlates of two strategies, encompassing behavioral and pharmacological approaches, aimed to interfere with the return of drug memories in individuals with cocaine use disorders. Results may pave the way towards enhancing the efficacy of cue-exposure therapy in reducing cue-induced craving and relapse in drug addiction (generalizable across drugs of abuse/behavioral addictions).

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Targeting Neural, Behavioral and Pharmacological Mechanisms of Drug Memories in Drug Addiction With Methylphenidate
• Actual Study Start Date: July 5, 2023
• Estimated Primary Completion Date: August 31, 2024
• Estimated Study Completion Date: August 31, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Methylphenidate then Placebo; 20 mg of methylphenidate then matching placebo pill.	Drug: Methylphenidate; Oral administration of 20 mg Methylphenidate; Behavioral: Memory reconsolidation; Retrieval of drug-cue memories before extinction.; Drug: Placebo; Matching placebo pill
Placebo Comparator: Placebo then Methylphenidate; Matching placebo pill then 20 mg of methylphenidate.	Drug: Methylphenidate; Oral administration of 20 mg Methylphenidate; Behavioral: Memory reconsolidation; Retrieval of drug-cue memories before extinction.; Drug: Placebo; Matching placebo pill

Outcome Measures

Primary Outcome Measures :

1. fMRI blood-oxygenation level dependent (BOLD) signal [ Time Frame: Day 1 ]
   fMRI blood-oxygenation level dependent (BOLD) signal deactivation in the ventromedial prefrontal cortex in response to retrieval of drug-cue memory.
2. fMRI blood-oxygenation level dependent (BOLD) signal [ Time Frame: Day 7 ]
   fMRI blood-oxygenation level dependent (BOLD) signal deactivation in the ventromedial prefrontal cortex in response to retrieval of drug-cue memory.

Secondary Outcome Measures :

1. Skin Conductance Responses (SCR) [ Time Frame: 24 hours after each neuroimaging session ]
   Measure of changes to skin conductance responses in response to retrieval of drug-cue memory. The conductance is measured by placing two electrodes on the fingers and passing a small, 0.5 V electric charge between the two points. An increase in the skin conductance response (SCR) reflects heightened arousal in response to the drug-cue memory, changes in which are monitored following exposure to the drug cues.
2. Craving [ Time Frame: 24 hours after each neuroimaging session ]
   Measure of changes to craving in response to retrieval of drug-cue memory. Self-reported cue-induced craving in response to drug cues will be assessed.

Eligibility Criteria

• Ages Eligible for Study: 26 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion criteria:

• Ability to understand and give informed consent
• Males and females 26-50 years of age
• DSM-V diagnosis for CUD or otherwise problematic cocaine use as clinically determined

Exclusion criteria:

• DSM-5 diagnosis for schizophrenia or developmental disorder (e.g., autism)
• Head trauma with loss of consciousness
• History of neurological disease of central origin including seizures
• Cardiovascular disease including high blood pressure and/or other medical conditions, including metabolic, endocrinological, oncological or autoimmune diseases, and infectious diseases including Hepatitis B and C or HIV/AIDS
• Metal implants or other MR contraindications

Contacts and Locations

Contacts

Contact: Natalie E McClain, BA; 5023034101; natalie.mcclain@mssm.edu

Locations

United States, New York

Icahn School of Medicine at Mount Sinai; Recruiting

New York, New York, United States, 10029

Sponsors and Collaborators

Icahn School of Medicine at Mount Sinai

National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Rita Z Goldstein, PhD; Icahn School of Medicine at Mount Sinai

More Information

• Responsible Party: Rita Goldstein, Chief of Research, Icahn School of Medicine at Mount Sinai
• ClinicalTrials.gov Identifier: NCT05978167
• Other Study ID Numbers: GCO 20-2707; R21DA054281 ( U.S. NIH Grant/Contract )
• First Posted: August 7, 2023
• Last Update Posted: August 7, 2023
• Last Verified: July 18, 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
• Supporting Materials: Study Protocol
• Time Frame: Immediately following publication. No end date.
• Access Criteria: Researchers who provide a methodologically sound proposal. Any purpose. Proposals should be directed to rita.goldstein@mssm.edu. To gain access, data requestors will need to sign a data access agreement.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Methylphenidate; Central Nervous System Stimulants; Physiological Effects of Drugs; Dopamine Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Dopamine Agents; Neurotransmitter Agents