Cocaine Dependence Treatment with Modafinil and Voucher-based Reinforcement Therapy in Methadone Maintenance (COMBAT-MM)

Lead Research Organisation: King's College London
Department Name: Unlisted

Abstract

Cocaine is a powerful illegal stimulant drug. Abuse of this drug is growing in the UK and there is a pressing need to develop effective treatment interventions. The use of crack cocaine (the smokeable form of the drug which can quickly lead to severe addiction) is widespread among heroin users seekers methadone maintenance treatment (MMT). In most instances their cocaine dependence is untreated. Consequently, we have designed a multi-centre, controlled clinical trial to investigate separately the efficacy of two interventions: (i) modafinil, a medication for narcolepsy which is promising for cocaine dependence; and (ii) voucher-based reinforcement therapy (VBRT), a motivational-incentive approach which promotes cocaine abstinence. This will be one of the largest trials of its kind treatment for cocaine dependence conducted internationally. At this point in the development of our work, we are seeking funding support from MRC to enable us to undertake pilot research to support our full application. This will enable us to conduct
3 studies: 1. A recruitment simulation. At each of five sites, a 6-month recruitment simulation will evaluate the overall referral rate; the proportion of patients with cocaine problems; the number of eligible patients for the trial; the reasons for non-eligibility or non-consent; the retention of these potential study subjects for at least 8 weeks; and outcome monitoring of cocaine use arising from MMT treatment-as-usual. 2(a). We will develop a clinical quality standard protocol for adherence s at each site and also a specific therapeutic manual for standard keyworker counselling. 2(b). We will implement a small-scale, uncontrolled VBRT pilot at the trial co-ordinating centre. 2(c). We will study how VBRT can shape reductions in cocaine use as a first step towards quitting. 3. Pilot-test alternative methods of urine drug-testing. We will test the feasibility of an on-site rather than external laboratory quantitative BE test procedure. Communication of results and their application. Our findings from the pilot will be communicated to MRC and summarised as part of the full application for support.

Technical Summary

Background. Cocaine misuse is a substantial and rapidly growing public health problem in the UK. NHS clinicians have no UK-based, research supported treatments to offer. There are no trials underway in the UK and there is a pressing need to develop effective interventions. Rationale. Cocaine dependence is induced and sustained by neurobiological adaptations and conditioned responses and is characterised by chronic compulsive drug taking. There is a strong theoretical rationale for a pharmacotherapy that can normalise specific neurotransmitter systems and a behavioural intervention that reinforces abstinence. The use of heroin and crack cocaine is widespread among heroin users seekers methadone maintenance treatment (MMT) but cocaine dependence is untreated. Aims, interventions and design. The proposed trial is designed to investigate separately the efficacy of two interventions for the treatment of cocaine dependence: (i) modafinil, a medication for narcolepsy which is promising for cocaine dependence; and (ii) voucher-based reinforcement therapy (VBRT), a motivational-incentive approach which promotes cocaine abstinence. The study will be a pragmatic, multi-centre, 2x2 factorial, medication double-blind, placebo controlled randomized clinical trial in with 8 weeks of treatment. Proposed pilot work. We understand from MRC that a competitive application should be supported by data on the ability of the clinical sites to recruit and retain patients. Our pilot will address this as well as other aspects of our protocol, in a series of 3 studies: 1. Recruitment simulation. At each of the five MMT recruitment sites, a 6-month recruitment simulation will evaluate the overall referral rate; the proportion of patients with cocaine problems; the number of eligible patients for the trial; the reasons for non-eligibility or non-consent; the retention of these potential study subjects for at least 8 weeks; and outcome monitoring of cocaine use arising from MMT treatment-as-usual (TAU). 2(a). We will develop a clinical quality standard protocol for adherence s at each site and also a specific therapeutic manual for standard TAU keyworker counselling. 2(b). We will implement a small-scale, uncontrolled VBRT pilot at the trial co-ordinating centre. 2(c). We will study how VBRT can shape reductions in cocaine use as a first step towards quitting. 3. Pilot-test alternative methods of urine drug-testing. We will test the feasibility of an on-site rather than external laboratory quantitative BE test procedure. Communication of results and their application. Our findings from the pilot will be communicated to MRC and summarised as part of the full application for support.

Publications

10 25 50
 
Description Generation of evidence for the feasibility of a multi-centre trial of pharmaco- and behaviour treatment for cocaine addiction 
Organisation Avon and Wiltshire Mental Health Partnership NHS Trust
Country United Kingdom 
Sector Public 
PI Contribution As the scientific coordinating centre (South London and Maudsley NHS trust and Institute of Psychiatry) we have developed the pilot patient recruitment protocol and monitored its implementation in London, Birmingham and Bristol. We have also developed a protocol for a behaviour therapy using contingency management to reinforce cocaine abstinence and piloted this in the trials' target population. Trial partners have met three times to discuss the scientific, organisational, management aspects.
Collaborator Contribution Clinical feasibility assessment (pilot patient recruitment) for the proposed trial (COMBAT). Adacemic input to the development of psychosocial and behaviour therapy intervention (protocol and therapy manual)Clinical feasibility assessment (pilot patient recruitment) for the proposed trial (COMBAT). Lead academic input to the development of psychosocial and behaviour therapy intervention (protocol and therapy manual).Clinical feasibility assessment (pilot patient recruitment) for the proposed trial (COMBAT). Academic input to the development of psychosocial and behaviour therapy intervention (protocol and therapy manual).Clinical feasibility assessment (pilot patient recruitment) for the proposed trial (COMBAT). Academic input to the development of psychosocial and behaviour therapy intervention (protocol and therapy manual)
Impact The main output is that we have successully undertaken the pilot feasibility study which will underpin our proposal for full trial funding.
Start Year 2008
 
Description Generation of evidence for the feasibility of a multi-centre trial of pharmaco- and behaviour treatment for cocaine addiction 
Organisation Central and North West London NHS Foundation Trust
Department Westminster Treatment Centre
Country United Kingdom 
Sector Public 
PI Contribution As the scientific coordinating centre (South London and Maudsley NHS trust and Institute of Psychiatry) we have developed the pilot patient recruitment protocol and monitored its implementation in London, Birmingham and Bristol. We have also developed a protocol for a behaviour therapy using contingency management to reinforce cocaine abstinence and piloted this in the trials' target population. Trial partners have met three times to discuss the scientific, organisational, management aspects.
Collaborator Contribution Clinical feasibility assessment (pilot patient recruitment) for the proposed trial (COMBAT). Adacemic input to the development of psychosocial and behaviour therapy intervention (protocol and therapy manual)Clinical feasibility assessment (pilot patient recruitment) for the proposed trial (COMBAT). Lead academic input to the development of psychosocial and behaviour therapy intervention (protocol and therapy manual).Clinical feasibility assessment (pilot patient recruitment) for the proposed trial (COMBAT). Academic input to the development of psychosocial and behaviour therapy intervention (protocol and therapy manual).Clinical feasibility assessment (pilot patient recruitment) for the proposed trial (COMBAT). Academic input to the development of psychosocial and behaviour therapy intervention (protocol and therapy manual)
Impact The main output is that we have successully undertaken the pilot feasibility study which will underpin our proposal for full trial funding.
Start Year 2008
 
Description Generation of evidence for the feasibility of a multi-centre trial of pharmaco- and behaviour treatment for cocaine addiction 
Organisation South London and Maudsley (SLAM) NHS Foundation Trust
Country United Kingdom 
Sector Academic/University 
PI Contribution As the scientific coordinating centre (South London and Maudsley NHS trust and Institute of Psychiatry) we have developed the pilot patient recruitment protocol and monitored its implementation in London, Birmingham and Bristol. We have also developed a protocol for a behaviour therapy using contingency management to reinforce cocaine abstinence and piloted this in the trials' target population. Trial partners have met three times to discuss the scientific, organisational, management aspects.
Collaborator Contribution Clinical feasibility assessment (pilot patient recruitment) for the proposed trial (COMBAT). Adacemic input to the development of psychosocial and behaviour therapy intervention (protocol and therapy manual)Clinical feasibility assessment (pilot patient recruitment) for the proposed trial (COMBAT). Lead academic input to the development of psychosocial and behaviour therapy intervention (protocol and therapy manual).Clinical feasibility assessment (pilot patient recruitment) for the proposed trial (COMBAT). Academic input to the development of psychosocial and behaviour therapy intervention (protocol and therapy manual).Clinical feasibility assessment (pilot patient recruitment) for the proposed trial (COMBAT). Academic input to the development of psychosocial and behaviour therapy intervention (protocol and therapy manual)
Impact The main output is that we have successully undertaken the pilot feasibility study which will underpin our proposal for full trial funding.
Start Year 2008
 
Description Generation of evidence for the feasibility of a multi-centre trial of pharmaco- and behaviour treatment for cocaine addiction 
Organisation University of Birmingham
Department College of Medical and Dental Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution As the scientific coordinating centre (South London and Maudsley NHS trust and Institute of Psychiatry) we have developed the pilot patient recruitment protocol and monitored its implementation in London, Birmingham and Bristol. We have also developed a protocol for a behaviour therapy using contingency management to reinforce cocaine abstinence and piloted this in the trials' target population. Trial partners have met three times to discuss the scientific, organisational, management aspects.
Collaborator Contribution Clinical feasibility assessment (pilot patient recruitment) for the proposed trial (COMBAT). Adacemic input to the development of psychosocial and behaviour therapy intervention (protocol and therapy manual)Clinical feasibility assessment (pilot patient recruitment) for the proposed trial (COMBAT). Lead academic input to the development of psychosocial and behaviour therapy intervention (protocol and therapy manual).Clinical feasibility assessment (pilot patient recruitment) for the proposed trial (COMBAT). Academic input to the development of psychosocial and behaviour therapy intervention (protocol and therapy manual).Clinical feasibility assessment (pilot patient recruitment) for the proposed trial (COMBAT). Academic input to the development of psychosocial and behaviour therapy intervention (protocol and therapy manual)
Impact The main output is that we have successully undertaken the pilot feasibility study which will underpin our proposal for full trial funding.
Start Year 2008
 
Title Contingency Management Protocol for Reinforcing Cocaine Abstinence 
Description Behaviour therapy protocol and staff training materials 
Type Therapeutic Intervention - Psychological/Behavioural
Current Stage Of Development Refinement. Clinical
Year Development Stage Completed 2009
Development Status On hold
Impact Intervention will be used in main trial 
 
Title psychosocial treatment intervention using mapping techniques 
Description novel, mapping technique to motivate recovery from addiction 
Type Therapeutic Intervention - Psychological/Behavioural
Current Stage Of Development Refinement. Clinical
Year Development Stage Completed 2009
Development Status Closed
Impact intervention will be delivered in the full trial