FORWARDS-1 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.

Volunteers taking part will be asked to attend two visits in total at the Imperial Clinical Research Facility (ICRF) in the Hammersmith Hospital. We will arrange taxi transport for all visits.

Study visit schedule

• Phone screening
• Visit 1: Consent and screening visit to check eligibility (2-3 hours).
• Visit 2: Experimental study day (~7 hours, approx. 09:30-16:00) when you are still taking your usual methadone dose.
• Follow-up phone check

At the experimental session, you will take your usual methadone prescription. You will then be given a medication to take, and you will undergo assessments including oxygen saturation, breathing rate and blood pressure monitoring. We will ask you to complete mood questionnaires (e.g. how the medication makes you feel). We will also take blood samples to measure levels of methadone and baclofen in your blood.

The medication will be a single dose of either baclofen or placebo (randomised in a 3:1 ratio). The dose will be recommended by a statistical model according to your personal methadone dose and according to previous safety data that we have collected in the study.

We will start with the lowest doses, then give increasing doses of baclofen (10mg, 30mg, 60mg, up to 90mg) to compare with placebo (dummy pill) if it is safe to do so. If a dose combination results in no adverse effects, the adaptive model will increase the next recommended baclofen dose level for the next person entering the study, according to that participant’s usual methadone dose. The model is regularly updated (after every 3 participants). This ensures that dose escalation only occurs if prior data suggest that it is safe to do so.

We are looking for male and female volunteers over the age of 21 who:

• Are currently taking stable doses of methadone for opioid dependence
• Are not currently dependent on any other drugs such as alcohol or cocaine*
• Are available 1 day per week for 2 weeks
• Are healthy as determined by a medical evaluation performed by a physician 

*Smokers are welcome

To register your interest and check your eligibility, please contact the team via the details provided above.

This study has been approved by the West of Scotland Research Ethics Service, REC number 21/WS/0080). It has been reviewed and funded by the Medical Research Council (MRC).

• Visit 1: £50
• Visit 2: £100
• Total: £150

We will also pay all travel expenses and provide lunch on the experimental day.

Recruitment is from Central and North West London NHS Foundation Trust (CNWL) and from ChangeGrowLive (CGL).

We are working with the following services operated by CNWL: 

• Brent Recovery Day Programme 
• New Beginnings (Brent) 
• Recovery Intervention Services Ealing (RISE) - Central Hub
• Recovery Intervention Services Ealing (RISE) - Southall 
• Addiction Recovery Community (ARC) Hounslow 
• Addiction, Recovery, Community, Hillingdon Service (ARCH) 

We are working with the following services operated by CGL:

• Camden Drug & Alcohol Services 
• Ealing RISE 
• Barnet