Deep brain stimulation for addiction
| ISRCTN | ISRCTN78042015 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN78042015 |
| IRAS number | 316169 |
| Secondary identifying numbers | IRAS 316169, CPMS 56678 |
- Submission date
- 09/07/2024
- Registration date
- 01/08/2024
- Last edited
- 14/11/2024
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Mental and Behavioural Disorders
Plain English Summary
Background and study aims
Alcohol and opioid addiction are major public health issues with significant personal and social costs and risks of physical and mental illness and early death. The disorders are associated with high relapse rates with many remaining refractory (not responding) to conventional therapies. Deep brain stimulation (DBS) acts like a brain pacemaker to normalise abnormal brain activity. It is effective for severe Parkinson's disease and other neurological disorders and for obsessive-compulsive disorder. DBS has been approved for use in tremor since 2002. More than a quarter of a million people worldwide have DBS devices implanted. A small randomised controlled trial and at least four pilot studies suggest both safety and potential effectiveness in alcohol and opioid use disorders. This study aims to use DBS to treat refractory alcohol and opioid addiction. Addictions can be considered an imbalance of excessive acceleration and lack of braking. DBS will stimulate the nucleus accumbens involved in the drive of motivation and reward for addictions and the ventral internal capsule white matter tracts involved in braking and decision-making to balance function.
Who can participate?
Adults (aged 18-60 years) with alcohol or opioid use disorder of at least 5 years duration, with at least three relapses, and who have failed conventional therapies
What does the study involve?
This is a 10-month study. DBS involves a neurosurgical procedure under general anaesthesia. The participant will stay in hospital for 7 to 10 days. The participant will be followed to optimise stimulation for 6 months then enter a 4-month randomised cross-over trial. They will also take part in brain recording studies to understand the disorder and to help optimise treatment. The DBS team will continue to follow the participant for as long as they have the device in place.
What are the benefits and risks of participating?
Severe untreated chronic addiction that is not responding to the usual treatments is at high risk of comorbid medical illness and early death. DBS has been approved since 2002 and has been shown to be relatively safe and effective in other neurological disorders and obsessive-compulsive disorder. More than a quarter million individuals have undergone DBS for other disorders. Specific to addictions, a small randomized controlled trial and several pilot studies also has shown DBS to be relatively safe and potentially effective. The risks of the neurosurgery can include infection, bleeding and seizure. The neurosurgical team are highly experienced functional neurosurgeons with the lead neurosurgeon having completed more than 500 DBS surgeries. Risks of stimulation include hypomania which can be managed by changing stimulation parameters.
Where is the study run from?
1. Cambridge University Hospital, University of Cambridge (UK)
2. Kings College Hospital, Kings College London (UK)
When is the study starting and how long is it expected to run?
January 2018 to January 2026
Who is funding the study?
The Medical Research Council (UK)
Who is the main contact?
1. Prof. Valerie Voon, vv247@cam.ac.uk
2. Dr David Okai
Contact information
Public, Scientific, Principal Investigator
University of Cambridge
Addenbrookes Hospital
Box 189 Level E4
Hills Road
Cambridge
CB2 0QQ
United Kingdom
 ORCID ID |
0000-0001-6790-1776 |
|---|---|
| Phone | +44 (0)1223 761 327 |
| vv247@cam.ac.uk |
Public
University of Cambridge
Addenbrookes Hospital
Box 189 Level E4
Hills Road
Cambridge
CB2 0QQ
United Kingdom
| ORCID ID |
0000-0003-0161-3995 |
|---|---|
| Phone | +44 (0)1223761327 |
| sns36@cam.ac.uk |
Study information
| Study design | Multicenter interventional double-blind randomized controlled crossover trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised cross over trial |
| Study setting(s) | Hospital, University/medical school/dental school |
| Study type | Treatment |
| Participant information sheet | 45761_PIS_V2.01_12Jan24.pdf |
| Scientific title | Deep brain stimulation for disorders of addiction: mechanisms and a pilot blinded randomized cross-over placebo-controlled trial |
| Study acronym | Brain-Pacer |
| Study hypothesis | Deep brain stimulation of the nucleus accumbens and ventral internal capsule is more effective than sham stimulation on alcohol and opioid use outcomes in alcohol and opioid use disorder. |
| Ethics approval(s) |
Approved 30/06/2023, Yorkshire and the Humber: Sheffield Research Ethics Committee (NHS Blood and Transplant Blood Donor Centre Holland Drive, Newcastle, NE2 4NQ, United Kingdom; +44 (0)207 104 8282; sheffield.rec@hra.nhs.uk), ref: 23/YH/0110 |
| Condition | Alcohol and opioid use disorder |
| Intervention | Following neurosurgical implantation, deep brain stimulation (DBS) will be delivered at chronic high frequency (~130 hz; 2-4 V) in the nucleus accumbens and ventral internal capsule. The stimulation protocol parameters will be optimized over the 6-month open-label stimulation optimization period. At postoperative month 6, participants will undergo a single-blind randomized cross-over controlled trial (order randomized) of four arms: dual stimulation, single stimulation and sham with each arm, lasting for 1 month. |
| Intervention type | Device |
| Pharmaceutical study type(s) | Not Applicable |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Deep brain stimulation |
| Primary outcome measure | Alcohol and opioid use is measured using Timeline Followback during randomised control cross-over trial at baseline and months 1, 2, 3 and 4 |
| Secondary outcome measures | Alcohol and opioid use is measured using Timeline Followback during open-label stimulation optimisation at baseline and months 1, 2, 3, 4, 5, 6 |
| Overall study start date | 01/01/2018 |
| Overall study end date | 31/01/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 60 Years |
| Sex | Both |
| Target number of participants | 12 |
| Participant inclusion criteria | 1. Diagnosis of treatment-refractory opioid use disorder (OUD) or alcohol use disorder (AUD) (DSM-5 diagnosis) 2. Comorbid nicotine dependence, other psychoactive use disorder permissible as long as OUD or AUD is the primary diagnosis 3. At least 5 years duration 4. 3+ failed abstinence attempts 5. Failed psychotherapy and standard pharmacotherapy 6. Age 18 to 60 years old 7. MRI compatible 8. Capable of informed consent |
| Participant exclusion criteria | 1. Deep brain stimulation or neurosurgical contraindication (e.g. unable to tolerate general anaesthesia, risk of bleeding) 2. History of repeated falls 3. Other major psychiatric (e.g. schizophrenia, bipolar disorder or severe major depression) or neurologic disorder 4. Major head injury 5. Marked cognitive impairment or cortical atrophy |
| Recruitment start date | 31/08/2023 |
| Recruitment end date | 31/08/2025 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Hills Road
Cambridge
CB2 0QQ
United Kingdom
London
SE5 8AB
United Kingdom
Beverley Road
Willerby Hill
Hull
HU10 6FE
United Kingdom
Sanderson House
17-19 Museum Street
Ipswich
IP1 1HE
United Kingdom
Sponsor information
Hospital/treatment centre
Hills Road
Cambridge
CB2 0QQ
England
United Kingdom
| Phone | +44 (0)1223 217418 |
|---|---|
| cuh.research@nhs.net | |
| Website | http://www.cuh.org.uk/ |
"ROR" |
https://ror.org/04v54gj93 |
University/education
Hills Road
Cambridge
CB2 0QQ
England
United Kingdom
| Phone | +44 (0)1223 217418 |
|---|---|
| cuh.research@nhs.net | |
| Website | http://www.cam.ac.uk/ |
|
"ROR" |
https://ror.org/013meh722 |
Funders
Funder type
Research council
Government organisation / National government
- Alternative name(s)
- Medical Research Council (United Kingdom), UK Medical Research Council, MRC
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/08/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Publication plans will include publication of the clinical trial data and mechanistic physiological studies. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be available upon request following publication from Prof. Valerie Voon (vv247@cam.ac.uk). |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version 2.01 | 12/01/2024 | 11/07/2024 | No | Yes |
Additional files
Editorial Notes
14/11/2024: Study website added.
09/07/2024: Study's existence confirmed by the HRA.
