FORWARDS-2 Study

Opiate addiction is a major health challenge. Treatment with opiate substitution treatment (OST; eg methadone or buprenorphine) and psychosocial support has been highly effective in improving health and social functioning. However, there is now a growing focus on abstinence, particularly for those who desire abstinence, or those who are older with increasingly complex physical and mental health needs; death rates involving opioids are now the highest in those aged 40-49 years old.

Achieving abstinence from chronic opioids typically involves undergoing detoxification. This generally involves slow tapering of OST with supportive medication to treat emerging symptoms. However, the efficacy of these ‘adjunct’ medications is limited and can usually only be used short-term and there have been no new medications to support opioid dependence in decades. It is therefore important to develop new treatments to assist detoxification that are suitable for community settings. We propose that the GABA-B agonist, baclofen, has the desired properties to facilitate opiate detoxification. Baclofen is likely to improve withdrawal symptoms including anxiety, insomnia, muscle aches, restless legs and craving. It is a generic medication that is licensed for spasticity and is currently used off-label to treat alcoholism so could be a viable treatment option for detoxification if it is shown to be safe and efficacious in methadone-maintained opiate dependence.

FORWARDS-1 

FORWARDS-1 seeks to investigate the safety of dose combinations of baclofen and methadone. Whilst our clinical experience and other studies suggest baclofen can be taken safely with methadone, they could potentially interact causing adverse effects such as respiratory depression. In addition, there is a possibility of individuals taking higher than recommended doses, so FORWARDS-1 will determine what are safe dose combinations of baclofen and methadone.

FORWARDS-2

Assuming we can safely combine baclofen and methadone at clinically relevant doses, we will then conduct a placebo-controlled, double-blind, randomized proof-of-concept trial to determine if baclofen is useful for facilitating detoxification from methadone in community-based opiate dependence. We aim to recruit only those who are committed to a community opiate detoxification pathway so that 56 complete this trial. Our aim will be to see whether baclofen produces a clinically meaningful reduction in methadone dose and increases abstinence rates. Data will be collected during the trial using validated measures eg opiate withdrawal, anxiety, sleep, restless legs. We will also collect information about adverse events and the feasibility of recruitment and retention. We will obtain data to design the definitive trial for which the primary outcome will be the proportion of participants successfully achieving abstinence.

• You will be involved in the study for up to 16 weeks (for some people this may be shorter)
• You would be randomly allocated to receive either baclofen or placebo (a placebo is a tablet which looks like the real thing but is not). You will take this study medication up to three times a day, in addition to your usual methadone dose.
• Every week you will be asked to complete a brief (5 minute) questionnaire, and receive a £5 voucher for each questionnaire completed on time.
• You will visit your local addiction service regularly to receive more study medication and answer some questions about your health and your feelings
• You will be invited to take part in an interview at the end of the study about your experience of taking part.
• Three months after your interview you will be contacted to review how you are doing since finishing the study

We are looking for male and female volunteers over the age of 18 who:

• Are currently taking a stable dose of methadone for opioid dependence
• Are not currently dependent on any other drugs such as alcohol or cocaine
• Wish to undergo methadone detoxification and/or dose reduction
  

This study has been approved by the West of Scotland Research Ethics Service, REC number 23/WS/0064. It has been reviewed and funded by the Medical Research Council (MRC).

You will be asked to complete up to 15 brief 5-minute questionnaires over the course of the study. You will receive a £25 voucher for attending and completing the Screening and Baseline visit, and a £25 voucher for attending and completing the Week 12 visit. For each questionnaire completed in a timely manner you will receive a £5 voucher.

Recruitment is from ChangeGrowLive (CGL); Central and North West London NHS Foundation Trust (CNWL),; Barnet, Enfield & Haringey Mental Health NHS Trust (BEH); Essex Partnership University NHS Foundation Trust (EPUT); Greater Manchester Mental Health NHS Foundation Trust (GMMH).

We are working with the following services operated by CNWL: 

• New Beginnings (Brent) 
• Recovery Intervention Services Ealing (RISE) - Central Hub
• Hillingdon
• Hounslow

We are working with the following services operated by CGL:

• Ealing RISE
• Manchester RISE
• Accrington
• Tameside My Recovery
• Wythenshawe (Bradnor Point)
• Waltham Forest

We are working with the following services operated by BEH:

• The Claverings
• Vincent House

We are working with the following services operated by EPUT:

• Chelmsford STARS
• Colchester STARS

We are working with the following services operated by GMMH:

• Achieve Bolton

Background

How service users, treatment providers, and service commissioners view detoxification (stopping methadone gradually) as a treatment for opioid dependence remains unclear. So, the main purpose of the AWARD study is to explore attitudes towards opioid substitution treatments and detoxification. 

Ethical approval

The AWARD study has been approved by the West of Scotland Research Ethics Service (REC number 23/WS/0064).

What's involved

If you decide to take part you will attend a single study visit (maximum 90minutes). This may take place using video conferencing software (e.g., Microsoft Teams), or in-person at your local addiction service, depending on your preference. You will be asked to:

• sign a paper or electronic Consent Form to confirm you agree to take part in the study.
• take part in an interview to discuss attitudes towards detoxification and treatments available for opioid dependence. This will be audio-recorded and saved under a code number (so you can't be identified)
• complete short questionnaires on your substance use and general health (service users only)

Am I eligible?

We are looking for volunteers over the age of 18 who:

• are currently taking methadone for opioid dependence at one of the FORWARDS-2 recruitment sites, or
• have recently stopped taking methadone for opioid dependence at one of the FORWARDS-2 recruitment sites, or
• provide treatment for people with opioid dependence at one of the FORWARDS-2 recruitment sites, or
• commission services that provide treatment for people with opioid dependence

Please refer to the Recruitment Partners tab above for a list of FORWARDS-2 recruitment sites.

Compensation

Service users (i.e., those receiving treatment for opioid dependence) will be compensated £40 for the study visit. Travel expenses will be reimbursed for all participants.