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Trial registered on ANZCTR


Registration number
ACTRN12614000859684
Ethics application status
Not yet submitted
Date submitted
30/07/2014
Date registered
11/08/2014
Date last updated
11/08/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
Anterior cingulate stimulation for alcohol addiction
Scientific title
Effect of anterior cingulate stimulation on craving in patients with severe alcohol use disorder
Secondary ID [1] 285082 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alcohol Use Disorder 292613 0
Condition category
Condition code
Mental Health 292927 292927 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A laterolateral frontal incision is made followed by a 4 cm x 4 cm right frontal craniotomy crossing the superior sagittal sinus. The dura is incised and two Lamitrode 44 electrodes (St Jude Medical, Plano, Dallas, TX) are placed interhemispherically, touching the rostral anterior cingulate cortices. This surgery may take ~2 hours.

Electrodes will be activated on Day 3 or Day 17 in a blinded manner. Stimulation patterns will be optimized over 1 week, initially with a 3 Hz burst stimulation with 5 spikes at 500 Hz in cycle mode (5 seconds on, 5 seconds off). The stimulation design can be individually adjusted to further optimize the anticraving effect. This might include burst or spike frequency adjustment, or switching to a noise-like pattern.

Electrodes will remain in place permanently.
Intervention code [1] 289921 0
Treatment: Surgery
Intervention code [2] 289955 0
Treatment: Devices
Comparator / control treatment
Patients will be randomized to early (Day 3 post-surgery) vs late (Day 17 post-surgery) start up of stimulation pattern.
Control group
Active

Outcomes
Primary outcome [1] 292792 0
Safety and tolerability (safety laboratory tests, vital signs and reported adverse events will be used to assess safety and tolerability throughout the study). Adverse events that might be related to neuromodulation include reduction in sustained attention or seizures.
Timepoint [1] 292792 0
12 weeks
Primary outcome [2] 292793 0
Alcohol craving self-rating (0-10 numeric rating scale)
Timepoint [2] 292793 0
12 weeks
Secondary outcome [1] 309693 0
Measures of alcohol intake (Timeline Follow Back; breath alcohol measurements; carbohydrate deficient transferrin, GGT and MCV).
Timepoint [1] 309693 0
12 weeks
Secondary outcome [2] 309694 0
Mood ratings (MADRS, State and Trait Anxiety)
Timepoint [2] 309694 0
12 weeks

Eligibility
Key inclusion criteria
1. Capable of understanding and signing an informed consent
2. Meeting DSM-5 severe Alcohol Use Disorder, based on a structured clinical interview with a consultant psychiatrist.
3. Primary addiction is to alcohol
4. Scoring >7 on the obsessive compulsive drinking scale.
5. Patients must have failed to respond to at least one residential alcohol treatment programme, at least one anticraving medication, and at least one outpatient intervention with specialist alcohol services.
6. Patients must be seeking help for their alcohol use disorder, and be willing to cooperate with surgical and psychiatric follow up.
7. Patients may remain on antidepressant or antianxiety medication during the study, but drugs and doses must remain unchanged from 6 weeks prior to surgery until 12 weeks post-surgery.
8. Patients must have a supportive social network (minimum 1 person) that they will provide contact details for, and involve in pre-/post-surgery appointments.
9. Patients must respond to rTMS with reduced alcohol craving (>50% reduction in craving numeric rating scale), using blinded placebo controlled testing
Minimum age
20 Years
Maximum age
60 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. History of epileptic seizures (except those associated with alcohol withdrawal)
2. Psychiatric disorders with psychotic symptoms or manic symptoms
3. Patients with pace makers/defibrillators
4. Patients who have contraindications for MRI
5. Female patients who are or intend to become pregnant
6. Participants who, in the opinion of the investigator, do not understand the information and procedures of the study, or would not be compliant with them (in particular the study restrictions and risks involved).
7. Any participant for whom the investigator believes, for any reason, that participation would not be an acceptable risk.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients will be sequentially allocated a subject number after completing screening and signing consent forms. Timing of activation of the electrode (early - day 3 post-surgery vs late - day 17) is double blind and randomized according to a computer-generated random code. Allocation will involve contacting the holder of the allocation schedule who will be “off-site”.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer-based random code generator
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Timing of activation of the electrode (early - day 3 vs late - day 17) is double blind and randomized according to a computer-generated random code.
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 6261 0
New Zealand
State/province [1] 6261 0

Funding & Sponsors
Funding source category [1] 289687 0
University
Name [1] 289687 0
University of Otago
Address [1] 289687 0
PO Box 56
Dunedin, 9054
New Zealand
Country [1] 289687 0
New Zealand
Primary sponsor type
University
Name
University of Otago
Address
Department of Neurosurgery
PO Box 56
Dunedin, 9054
New Zealand
Country
New Zealand
Secondary sponsor category [1] 288382 0
Commercial sector/Industry
Name [1] 288382 0
St Jude Medical, Neurodivision
Address [1] 288382 0
6901 Preston Road
Plano, TX 75024
Country [1] 288382 0
United States of America

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 291428 0
Health and Disability Ethics Committee
Ethics committee address [1] 291428 0
Ministry of Health
No 1 The Terrace
PO Box 5013
Wellington
Ethics committee country [1] 291428 0
New Zealand
Date submitted for ethics approval [1] 291428 0
01/09/2014
Approval date [1] 291428 0
Ethics approval number [1] 291428 0

Summary
Brief summary
Alcohol craving may be a major factor in why some patients with severe alcoholism can't stop drinking, or relapse after a period of abstinence. This craving may be caused by abnormally increased activation of a part of the brain (the anterior cingulate cortex). It may be possible to suppress craving and thus help abstinence from alcohol, by using neuromodulation methods. Initially we would identify patients who have reduced craving in response to transcranial magnetic stimulation of this brain area. Patients could then have an electrode implanted that could help maintain long-term abstinence from alcohol, and may also potentially help improve symptoms of depression and anxiety.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 50322 0
Prof Dirk de Ridder
Address 50322 0
Dunedin School of Medicine
PO Box 56
Dunedin 9054
Country 50322 0
New Zealand
Phone 50322 0
+64 3 474 0999
Fax 50322 0
+64 3 470 9901
Email 50322 0
dirk.deridder@otago.ac.nz
Contact person for public queries
Name 50323 0
Prof Dirk de Ridder
Address 50323 0
Dunedin School of Medicine
PO Box 56
Dunedin 9054
Country 50323 0
New Zealand
Phone 50323 0
+64 3 474 0999
Fax 50323 0
+64 3 470 9901
Email 50323 0
dirk.deridder@otago.ac.nz
Contact person for scientific queries
Name 50324 0
Prof Patrick Manning
Address 50324 0
Dunedin School of Medicine
PO Box 56
Dunedin 9054
Country 50324 0
New Zealand
Phone 50324 0
+64 3 474 0999
Fax 50324 0
+64 3 470 9901
Email 50324 0
Patrick.Manning@southerndhb.govt.nz

No data has been provided for results reporting
Summary results
Not applicable