A Trial of Long-Acting Injectable Risperidone in the Treatment of Methamphetamine Dependence

Methamphetamine Dependence Clinical Trial

Official title:

An Open-Label Trial of Long-Acting Injectable Risperidone in the Treatment of Methamphetamine Dependence

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00284206
• Other study ID #: RIS-NAP-4008
• Status: Completed
• Phase: Phase 2
• First received: January 27, 2006
• Last updated: January 3, 2008
• Start date: January 2006
• Est. completion date: August 2007

Study information

• Verified date: January 2008
• Source: Seattle Institute for Biomedical and Clinical Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Objective of the Project.

-Methamphetamine (MA) use is growing to epidemic proportions and existing treatments for MA dependence demonstrate sub-optimal efficacy. Research implicates heavy use of MA as at least a contributing agent to a variety of neuropsychiatric impairments including psychosis, mood disturbance, anxiety, cognitive deficits, and motor dysfunction. Initial study by this investigator suggests that agents like risperidone may also be beneficial to MA dependent individuals by decreasing MA use and improving cognitive function in early abstinence. Long-acting injectable risperidone may prove more efficacious given its receptor binding characteristics and potential to increase medication adherence. The study objective is to determine the safety and efficacy of treating MA dependence and the associated cognitive and psychiatric symptomatology with long-acting injectable risperidone.

Description:

Objective of the Project.

-Methamphetamine (MA) use is growing to epidemic proportions and existing treatments for MA dependence demonstrate sub-optimal efficacy. Research implicates heavy use of MA as at least a contributing agent to a variety of neuropsychiatric impairments including psychosis, mood disturbance, anxiety, cognitive deficits, and motor dysfunction. Initial study by this investigator suggests that agents like risperidone may also be beneficial to MA dependent individuals by decreasing MA use and improving cognitive function in early abstinence. Long-acting injectable risperidone may prove more efficacious given its receptor binding characteristics and potential to increase medication adherence. The study objective is to determine the safety and efficacy of treating MA dependence and the associated cognitive and psychiatric symptomatology with long-acting injectable risperidone.

Research Plan.

-This is an open-label trial of long-acting injectable risperidone administered 25mg every 2-weeks for the treatment of methamphetamine (MA) dependence. Participation will last approximately 14 weeks. A total of 20 subjects (veterans and non-veterans) aged 18 to 65 years old who meet DSM-IV criteria for current MA dependence, have a stable address or alternative contact, and expect to be in the Puget Sound area for the length of the study will be enrolled at the Seattle and American Lake Divisions of the VA PSHCS. Exclusionary criteria include: 1) known sensitivity or allergy to risperidone; 2) current treatment with an antipsychotic agent, a mood stabilizer, or CYP 2D6 inhibitor; (3) transaminase levels >5X ULN; (4) albumin levels <3.5g/dl; (5) random serum glucose levels >200mg/dl; (6) diabetes mellitus or history of myocardial infarction; (7) baseline Brief Psychiatric Rating Scale score >72; (8) presence of tardive dyskinesia; (9) Barnes Akathisia Rating Scale global item score >2; (10) Simpson-Angus Scale total score > 0.3; (11) involvement with the legal system that could compromise study participation; (12) pregnancy or nursing; (13) receiving current mental health treatment.

Methodology

-Potential subjects will complete a screening, including medical history and physical, laboratory, EKG, assessment of MA and other drug use, psychiatric screening and cognitive testing, to determine eligibility. Eligible subjects will repeat the cognitive testing instruments prior to starting medication. After completing the screening period, subjects who continue to be eligible will receive 7 days of oral risperidone to assess tolerability followed by administration of long-acting injectable risperidone, 25mg. For 3 weeks following the first IM injection, participants will take oral risperidone each night to achieve a therapeutic plasma level of risperidone. During the oral co-administration phase, participants will have medication pill counts during their weekly visit to evaluate adherence and corroborate self-report data. Participants will receive additional 25mg risperidone injections every 14 days (at weeks 2, 4, and 6 after the first injection).

Following the first injection, subjects will return to the study center for weekly visits for 8 weeks. At each study visit, patients will be evaluated for possible adverse events, use of concomitant medications, and use of methamphetamine. Safety labs will be repeated at week 4 and 8. Plasma levels of risperidone and 9-OH-risperidone will be obtained at 3, 6, and 8 weeks. If intolerable adverse events occur, risperidone dosage will be reduced, or, if indicated, risperidone will be discontinued. Psychiatric symptoms and cognitive functioning will be evaluated at Baseline, and 4 and 8 weeks. A follow-up visit will take place at 12 weeks. Subjects will receive behavioral treatment consisting of individual, once weekly, standardized, manual guided, relapse prevention therapy.

Findings, results, or conclusions reached to date.

-None to date.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: August 2007
• Est. primary completion date: August 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Meets DSM-IV criteria for methamphetamine (MA) dependence during the past year with current MA use within the 30-days prior to study entry

• Plans to remain in the Puget Sound area for the following 12 weeks

• If female of child bearing potential, agreeable to using an adequate method of birth control

• Age 18-65 years old

• Willing and capable of providing informed consent

• Presence of one or more of the following: stable address, telephone number, or alternative contact person

Exclusion Criteria:

• Known sensitivity or allergy to risperidone

• Current treatment with an antipsychotic agent

• Current treatment with a mood stabilizer

• Current treatment with a CYP 2D6 inhibitor (includes Amiodarone, Bupropion, Celecoxib, Cimetidine, Chlorpromazine, Clomipramine, Fluoxetine, Haloperidol, Methadone, Moclobemide, Paroxetine, Quinidine, Ritonavir, Sertraline, Terbinafine and Thioridazine)

• Presence of tardive dyskinesia

• A global item score >2 on the Barnes Akathisia Rating Scale.

• A total score on the Simpson-Angus Scale > 0.3.

• Albumin level <3.5g/dl.

• Random serum glucose level >200mg/dl.

• Transaminase levels > 5X ULN

• Presence of one or more of the following medical conditions: diabetes mellitus or history of myocardial infarction.

• A total score on the Brief Psychiatric Rating Scale >72.

• Involvement with the legal system that could compromise study participation

• Pregnancy or nursing

• Receiving concurrent mental health treatment in addition to the study

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Methamphetamine Dependence

Intervention

Drug:
• long-acting injectable risperidone

Locations

Country	Name	City	State
United States	VA Puget Sound Health Care System, Addictions Treatment Center	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Seattle Institute for Biomedical and Clinical Research	Janssen, LP

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy will be assessed by obtaining weekly self-report measures of MA and other substance use via the timeline follow-back interview corroborated with weekly urine toxicology specimens for substances of abuse including amphetamines.
Secondary	Secondary efficacy measures include:
Secondary	changes in neuropsychological performance,
Secondary	changes in psychiatric symptomatology,
Secondary	by changes in addiction severity