Facilitating detoxification and dose reduction from methadone using baclofen

Plain English summary of protocol

Background and study aims
Opioid addiction remains a major challenge in the UK. Opioid substitution therapy (OST), usually methadone, is associated with reduced illicit heroin use and health improvements. When someone desires abstinence, their methadone dose is gradually reduced over weeks to reduce the risk of withdrawal symptoms. However, many find ‘detoxification’ difficult to tolerate due to sleep disturbance, anxiety and fear of experiencing withdrawal. These symptoms can be eased with medications, such as lofexidine, but it is no longer available in the UK so new treatments are needed.
Evidence suggests that a GABA-B agonist, baclofen, may be helpful in reducing opiate withdrawal symptoms. Baclofen is a licensed medication to treat muscle spasms. The FORWARDS-1 study established that individuals on methadone (up to 70 mg/day) could safely take 60 mg of baclofen. This study is investigating whether baclofen can help people reduce or stop their methadone.

Who can participate?
Opioid-dependent participants who wish to undergo dose reduction or detoxification from methadone

What does the study involve?
Participants will be randomly allocated to receive baclofen or placebo, alongside the usual treatment. The baclofen dose will be increased over 7-10 days to achieve a maintenance dose of 30-60 mg/day for up to 12 weeks. Participants will attend regular in-person visits and complete weekly brief questionnaires about how they are feeling while taking the study medication. Methadone dose, medication compliance, side effects and feasibility measures will be recorded at each visit. After 12 weeks every participant will have their study medication withdrawn over 7-14 days and then complete an exit questionnaire about their experience of the trial. With consent, we will contact them 3 months later to see how they are. If the trial is shown to be feasible and baclofen shows promise as a medication to assist detoxification or dose reduction, we will design a full trial to test its effectiveness.

What are the possible benefits and risks of participating?
Participants may benefit from taking part by achieving methadone dose reduction or abstinence from methadone. The results of the study may help improve the treatment of people with opiate dependence in future.
All opiate-dependent participants will be under the care of a specialist clinical service for addictions, and therefore be receiving support and know how to access extra support if required. In order to undergo detoxification or dose reduction from their methadone, individuals must be engaged with such a service, often attending appointments regularly for many months and receiving psychosocial support, generally not using or very limited on-top use of heroin or other drugs and have a stable and supportive living situation. With the individual, the clinical team will make the decision if detoxification/dose reduction is appropriate. This will reduce any potential risk (e.g. relapse) of an individual starting before they are ready as the service will know the individual well.
The clinical teams identifying potential participants will be in close contact with the research team at Imperial College if there are any concerns about participants’ suitability to take part in the study or any changes in circumstances post-screening.
No treatment is withheld from participants in this study, as the addition of baclofen or placebo is an adjunct to treatment as usual, and they remain on their dose of methadone until such time as their treating psychiatrist/doctor deems it appropriate to adjust their dose.
Participants will be regularly asked about their physical and mental health during the study. The baseline interview will include questions on personal history, substance use and recovery plans. This may bring up sensitive or triggering issues, but they are relevant to any study of drug dependence. The local addiction service where the interviews will take place will be able to provide support and guidance to help reduce any concerns.
Individuals in treatment are regularly asked about how they are feeling and any difficulties they may be experiencing. The lengthier questionnaires will take place in clinic or over the phone with their key worker or member of the research staff who will be able to offer advice or support or direct them to access appropriate support as required. Online questionnaires completed at their convenience will be much shorter and will include a reminder to contact their local service if they need any support or assistance.
The GABA-B receptor agonist, baclofen, is a licensed medication with a very good tolerability and safety profile. The dose used in this study (up to 20 mg tds) is lower than the usual dose prescribed for spasticity (100 mg) and is commensurate with that used to treat alcoholism. From our clinical and research experience with baclofen, we do not experience any issues from this dose. To mitigate any side effects, why participants are advised to take their baclofen or placebo three times a day, with meals, to reduce the impact of this.
The SmPC raises the issue of potential misuse, abuse and dependence for baclofen. We are aware of this and are monitoring participants regularly during the trial including measures of medication compliance, adherence and subjective effects, and participants and staff have access to a 24-hour phone line to seek advice and to report any issues. Participants also receive care and support from their clinical addiction service which is experienced in identifying, assessing and managing such issues.
As baclofen is not routinely prescribed to this particular patient population or administered alongside opiate substitute medication there are specific considerations. In the preceding FORWARDS-1 trial (completed December 2022) we established it is safe to co-prescribe doses of up to 70mg methadone per day with up to 60 mg baclofen so we believe these risks are low due to clinical experience and previous studies. Baclofen is not contraindicated in hepatitis C or liver dysfunction that may be present in opiate addicts.
As with all such clinical trials there are safety risks, but they will be minimised as much as possible by obtaining safety parameters around combination use and instructing clinicians to use a pragmatic approach to dosing in the trial, and using well-trained staff and adherence to established safety protocols and SOPs.

Where is the study run from?
Imperial College London (UK)

When is the study starting and how long is it expected to run for?
March 2023 to March 2026

Who is funding the study?
Medical Research Council (UK)

Who is the main contact?
Dr Louise Paterson, l.paterson@imperial.ac.uk

Contact information

Study information

Eligibility

Locations

Countries of recruitment

• United Kingdom
• England

Study participating centres

Results and Publications

Study outputs

Editorial Notes

06/10/2025: The following changes were made to the trial record:
1. The completion date was changed from 31/12/2025 to 31/03/2026.
2. The study participating centres were updated.
09/06/2025: The recruitment end date was changed from 30/06/2025 to 31/10/2025.
05/03/2025: The following changes were made to the study record:
1. The recruitment end date was changed from 31/03/2025 to 30/06/2025.
2. The overall study end date was changed from 31/05/2025 to 31/12/2025.
07/02/2024: Internal review.
26/10/2023: ISRCTN received notification of combined HRA/MHRA approval for this trial on 26/10/2023.
04/04/2023: Trial's existence confirmed by the HRA.