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

Tracking Information

• First Submitted Date: July 28, 2023
• First Posted Date: August 7, 2023
• Last Update Posted Date: August 7, 2023
• Actual Study Start Date: July 5, 2023
• Estimated Primary Completion Date: August 31, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 28, 2023)

• 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.
• 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.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: July 28, 2023)

• 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.
• 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Targeting Drug Memories With Methylphenidate
• Official Title: Targeting Neural, Behavioral and Pharmacological Mechanisms of Drug Memories in Drug Addiction With Methylphenidate
• 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.
• 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 Type: Interventional
• Study Phase: Early Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment

Condition

• Substance Use Disorder
• Cocaine Use Disorder

Intervention

• Drug: Methylphenidate
  Oral administration of 20 mg Methylphenidate
• Behavioral: Memory reconsolidation
  Retrieval of drug-cue memories before extinction.
• Drug: Placebo
  Matching placebo pill

Study Arms

• Experimental: Methylphenidate then Placebo
  20 mg of methylphenidate then matching placebo pill.
  Interventions:

  • Drug: Methylphenidate
  • Behavioral: Memory reconsolidation
  • Drug: Placebo
• Placebo Comparator: Placebo then Methylphenidate
  Matching placebo pill then 20 mg of methylphenidate.
  Interventions:

  • Drug: Methylphenidate
  • Behavioral: Memory reconsolidation
  • Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 28, 2023): 50
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 31, 2024
• Estimated Primary Completion Date: August 31, 2024 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 26 Years to 50 Years (Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05978167
• Other Study ID Numbers: GCO 20-2707; R21DA054281 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

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.

• Current Responsible Party: Rita Goldstein, Icahn School of Medicine at Mount Sinai
• Original Responsible Party: Same as current
• Current Study Sponsor: Icahn School of Medicine at Mount Sinai
• Original Study Sponsor: Same as current
• Collaborators: National Institute on Drug Abuse (NIDA)

Investigators

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

• PRS Account: Icahn School of Medicine at Mount Sinai
• Verification Date: July 18, 2023