Primary Alcohol Use DisorderPhase 2KARENCT02649231

Ketamine for Reduction of Alcoholic Relapse

A Phase 2 study testing Ketamine, Psychological Therapy and Alcohol Education in people with Primary Alcohol Use Disorder, run by University College, London at 2 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 60 years
Conditions the study is for: Primary Alcohol Use Disorder
What is being tested?: Ketamine, Psychological Therapy and Alcohol Education
Type of treatment: Lifestyle or therapy programme
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 96 participants
Where: 2 sitesUnited Kingdom
Study dates: Oct 2016to Feb 2020
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 60 years
All sexes
No healthy volunteers
Adult

Who may be able to join

Meet either a) DSM-5 criteria for severe alcohol use disorder and b) DSM-IV criteria for alcohol dependence within the last 12 months;
Currently abstinent from alcohol (breathalyser BAC level 0.00) and negative urine drug screening (participants testing positive for THC who do not have a history or current cannabis dependency may be included);
Minimum of mild depression(>14 on Beck Depression Inventory-II);
Capacity to give informed consent as defined by GCP guidelines;
Willing and able to wear SCRAM-X bracelet for 6 months;
Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; True abstinence) from the time consent is signed until 6 weeks after treatment discontinuation and inform the trial if pregnancy occurs. For the purpose of clarity, True abstinence is when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence, withdrawal, spermicides only or lactational amenorrhoea method for the duration of a trial, are not acceptable methods of contraception;
Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for trial treatment and on day of first treatment.

Who cannot join

Currently taking any other relapse prevention medication or anti-depressants;
Uncontrolled hypertension, systolic 140mm Hg or greater and diastolic 90mm Hg or greater;
<16 or > 35 BMI
History of psychosis, or in a first-degree relative as identified by DSM-5 or DSM-IV SCID; co-morbid current psychiatric diagnosis excluding depression, identified via self-reported or identified by a medical professional;
Previous or current diagnosis of substance dependence / severe substance misuse disorder;
History of neuropsychological difficulties

Show all 37Show fewer

One or more previous confirmed seizures;
Currently taking daily prescribed medication contraindicated in the SPC with ketamine:
Barbiturates and/or narcotics
Atracurium and tubocurarine
Central nervous system (CNS) depressants (e.g. phenothiazines, sedating H1 - blockers or skeletal muscle relaxants)
Anxiolytics, sedatives and hypnotics
Thiopental, thyroid hormones
Antihypertensive agents
Theophylline and methylxanthines.
Halogenated anaesthetics
OR psychotropic drug use at screening assessments or during treatment weeks
Liver function tests > 3 times normal levels
Where there are "special warnings or precautions for use" according to the SPC and where risk vs benefit ratio is not in favour of giving ketamine, with assessment made by physical examination by medically qualified trial personnel, self-report or inspection of the medical notes:
Acute intermittent porphyria
Dehydration or hypovolemia
Hyperthyroidism, or patients receiving thyroid replacement
Pulmonary or upper respiratory tract infection
Severe Coronary artery disease, Cerebrovascular accident or cerebral trauma
Diabetes
Known glaucoma or globe injuries
Cirrhosis
Epilepsy
Neurological condition/brain damage
Intracranial mass lesions, presence of head injury or hydrocephalus
Suicidal ideation.
Not willing to use effective contraception or (females) take pregnancy test;
Allergic reaction to ketamine;
>10 previous detoxifications from alcohol;
Pregnant or breastfeeding;
Allergies to excipients of IMP or placebo;
Use of another experimental investigational medicinal product that is likely to interfere with the study medication within 3 months of study enrolment.

Trial locations and contacts

2 sites in 1 country.

United Kingdom2 sites

NIHR Exeter Clinical Research Facility
Exeter, EX4 5DW
NIHR UCLH Clinical Research Facility
London, NW1 2BU

Other trials in United Kingdom

About this study

Official title: A Phase II, Randomised, Double-blind, Placebo- Controlled, Multi-site, Parallel Group Clinical Trial to Examine Ketamine as a Pharmacological Treatment for Alcohol Dependence in an Alcohol Dependent Population

96 recently detoxified alcoholics will be randomized to receive either 3 sessions ketamine (0.8 mg/kg IV over 45 minutes) or placebo plus manualised psychological therapy, or 3 sessions of ketamine or placebo plus simple psychoeducation. Patients will be assessed at 3 and 6 months on a range of psychological and biological variables. Primary endpoints will be % days abstinent at 6 months and relapse rates at 6 months. Secondary endpoints include depressive symptoms, craving, quality of life.

Conditions: Primary Alcohol Use Disorder
Being tested: Ketamine, Placebo, Psychological Therapy, Alcohol Education

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

KetamineDrug
0.8 mg/kg ketamine
PlaceboDrug
0.9% saline
Psychological TherapyBehavioural
Manualised relapse prevention based CBT
Alcohol EducationBehavioural
Simple education about alcohol effects

Study groups in NCT02649231
Study group	Role	What they receive
Ketamine+Psychological Therapy	Experimental	Ketamine with psychological therapy Receives: Drug: Ketamine; Behavioral: Psychological Therapy
Ketamine+Education	Active comparator	ketamine with alcohol education Receives: Drug: Ketamine; Behavioral: Alcohol Education
Placebo+Psychological Therapy	Active comparator	placebo with psychological therapy Receives: Drug: Placebo; Behavioral: Psychological Therapy
Placebo+Education	Placebo comparator	placebo with simple alcohol education Receives: Drug: Placebo; Behavioral: Alcohol Education

What is being measured

The primary outcome is the main question the study is designed to answer.

Relapse Rates
Time line follow back
Measured: 6 months
Percentage Days Abstinent
Time line follow back
Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2016Feb 2020

First posted7 Jan 2016 (estimated)
Study startOct 2016
Primary completionFeb 2020
Study completionFeb 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Primary Alcohol Use DisorderStudies of the same condition, open and under way.
More trials run by University College, LondonThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 96 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02649231
Sponsor's protocol ID: 13/0253.
Acronym: KARE
Status last verified: Sep 2021
First submitted: 5 Jan 2016
Last updated: 5 Oct 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Grabski M, McAndrew A, Lawn W, Marsh B, Raymen L, Stevens T, Hardy L, Warren F, Bloomfield M, Borissova A, Maschauer E, Broomby R, Price R, Coathup R, Gilhooly D, Palmer E, Gordon-Williams R, Hill R, Harris J, Mollaahmetoglu OM, Curran HV, Brandner B, Lingford-Hughes A, Morgan CJA. Adjunctive Ketamine With Relapse Prevention-Based Psychological Therapy in the Treatment of Alcohol Use Disorder. Am J Psychiatry. 2022 Feb;179(2):152-162. doi: 10.1176/appi.ajp.2021.21030277. Epub 2022 Jan 11.
PubMed 35012326
Grabski M, Borissova A, Marsh B, Morgan CJA, Curran HV. Ketamine as a mental health treatment: Are acute psychoactive effects associated with outcomes? A systematic review. Behav Brain Res. 2020 Aug 17;392:112629. doi: 10.1016/j.bbr.2020.112629. Epub 2020 May 30.
PubMed 32485203
McAndrew A, Lawn W, Stevens T, Porffy L, Brandner B, Morgan CJ. A proof-of-concept investigation into ketamine as a pharmacological treatment for alcohol dependence: study protocol for a randomised controlled trial. Trials. 2017 Apr 4;18(1):159. doi: 10.1186/s13063-017-1895-6.
PubMed 28372596

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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The ICEC Cluster Trial: Integrated Community Engagement Collaborative for Youth Substance Use Prevention in Rural America
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A Female-Specific CBT Group for Veteran Women With Alcohol Use Disorder in VA Primary Care Settings
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Not yet recruiting
Snoezelen Therapy in Adults With Alcohol Dependence and Adults With Schizophrenia
SCHIZOPHRENIA 1 (Disorder), Alcohol Use Disorder

All Primary Alcohol Use Disorder trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase II, Randomised, Double-blind, Placebo- Controlled, Multi-site, Parallel Group Clinical Trial to Examine Ketamine as a Pharmacological Treatment for Alcohol Dependence in an Alcohol Dependent Population
ClinicalTrials.gov ID: NCT02649231
Acronym / sponsor ID: KARE / 13/0253.
Conditions: Primary Alcohol Use Disorder
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 96 participants (actual)
Lead sponsor: University College, LondonUniversity, hospital or other
Study start: Oct 2016 (actual)
Primary completion: Feb 2020 (actual)
Study completion: Feb 2020 (actual)
First posted: 7 Jan 2016 (estimated)
Results: Posted 9 Sep 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
Ketamine+Psychological Therapy	Experimental	Drug: Ketamine, Behavioral: Psychological TherapyKetamine with psychological therapy
Ketamine+Education	Active comparator	Drug: Ketamine, Behavioral: Alcohol Educationketamine with alcohol education
Placebo+Psychological Therapy	Active comparator	Drug: Placebo, Behavioral: Psychological Therapyplacebo with psychological therapy
Placebo+Education	Placebo comparator	Drug: Placebo, Behavioral: Alcohol Educationplacebo with simple alcohol education

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (7 listed)

Meet either a) DSM-5 criteria for severe alcohol use disorder and b) DSM-IV criteria for alcohol dependence within the last 12 months;
Currently abstinent from alcohol (breathalyser BAC level 0.00) and negative urine drug screening (participants testing positive for THC who do not have a history or current cannabis dependency may be included);
Minimum of mild depression(>14 on Beck Depression Inventory-II);
Capacity to give informed consent as defined by GCP guidelines;
Willing and able to wear SCRAM-X bracelet for 6 months;

Key exclusion criteria (37 listed)

Currently taking any other relapse prevention medication or anti-depressants;
Uncontrolled hypertension, systolic 140mm Hg or greater and diastolic 90mm Hg or greater;
<16 or > 35 BMI
History of psychosis, or in a first-degree relative as identified by DSM-5 or DSM-IV SCID; co-morbid current psychiatric diagnosis excluding depression, identified via self-reported or identified by a medical professional;
Previous or current diagnosis of substance dependence / severe substance misuse disorder;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Ketamine0.8 mg/kg ketamine	Drug	Ketamine+Education, Ketamine+Psychological Therapy
Placebo0.9% saline	Drug	Placebo+Education, Placebo+Psychological Therapy
Psychological TherapyManualised relapse prevention based CBT	Behavioural	Ketamine+Psychological Therapy, Placebo+Psychological Therapy
Alcohol EducationSimple education about alcohol effects	Behavioural	Ketamine+Education, Placebo+Education

Primary outcome

Relapse Rates
Time frame: 6 months
Time line follow back
Percentage Days Abstinent
Time frame: 6 months
Time line follow back

Results and safety

Results posted to the registry on 9 Sep 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ketamine+Psychological Therapy	24	20
Ketamine+Education	24	21
Placebo+Psychological Therapy	23	21
Placebo+Education	25	23

Primary outcome: Relapse Rates

Time frame: 6 months. Count of participants. Unit: Participants

Measure	Ketamine+Psychological Therapy n = 21	Ketamine+Education n = 22	Placebo+Psychological Therapy n = 21	Placebo+Education n = 23
Value	13	15	14	18

Ketamine+Psychological Therapy vs Ketamine+Education vs Placebo+Psychological Therapy vs Placebo+Education: Odds Ratio (OR): 0.7 (95% CI 0.28 to 1.75)

Population analysed: To explain discrepancies between overall number of participants analysed and the flow diagram: Only participants with a minimum of 159 days of completed drinking self-report data were included in the main analysis of alcohol relapse status as this was the shortest duration of time before any participant completed the 6 month (23-25 week) follow up in the study. Reporting time was capped at 180 days.

Primary outcome: Percentage Days Abstinent

Time frame: 6 months. Mean (Standard Deviation). Unit: percentage of days abstinent

Measure	Ketamine+Psychological Therapy n = 24	Ketamine+Education n = 24	Placebo+Psychological Therapy n = 23	Placebo+Education n = 25
Value	86.4 (17.7)	82.5 (20.0)	78.3 (26.9)	70.7 (25.1)

Ketamine+Psychological Therapy vs Ketamine+Education vs Placebo+Psychological Therapy vs Placebo+Education: Mean Difference (Final Values): 10.1 (95% CI 1.1 to 19.0)

Adverse events

Time frame: Screening visit (visit 1) to 6 month follow-up visit (visit 10).Participants were asked about any potential adverse events at the beginning of each visit.. Other adverse events reported at 4% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ketamine+Psychological Therapy	0 of 24 (0%)	13 of 24 (54.2%)	0 of 24
Ketamine+Education	0 of 24 (0%)	17 of 24 (70.8%)	0 of 24
Placebo+Psychological Therapy	2 of 23 (8.7%)	16 of 23 (69.6%)	0 of 23
Placebo+Education	1 of 25 (4%)	17 of 25 (68%)	0 of 25

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 35012326Grabski M, McAndrew A, Lawn W, Marsh B, Raymen L, Stevens T, Hardy L, Warren F, Bloomfield M, Borissova A, Maschauer E, Broomby R, Price R, Coathup R, Gilhooly D, Palmer E, Gordon-Williams R, Hill R, Harris J, Mollaahmetoglu OM, Curran HV, Brandner B, Lingford-Hughes A, Morgan CJA. Adjunctive Ketamine With Relapse Prevention-Based Psychological Therapy in the Treatment of Alcohol Use Disorder. Am J Psychiatry. 2022 Feb;179(2):152-162. doi: 10.1176/appi.ajp.2021.21030277. Epub 2022 Jan 11.
Derived from this study: PubMed 32485203Grabski M, Borissova A, Marsh B, Morgan CJA, Curran HV. Ketamine as a mental health treatment: Are acute psychoactive effects associated with outcomes? A systematic review. Behav Brain Res. 2020 Aug 17;392:112629. doi: 10.1016/j.bbr.2020.112629. Epub 2020 May 30.
Derived from this study: PubMed 28372596McAndrew A, Lawn W, Stevens T, Porffy L, Brandner B, Morgan CJ. A proof-of-concept investigation into ketamine as a pharmacological treatment for alcohol dependence: study protocol for a randomised controlled trial. Trials. 2017 Apr 4;18(1):159. doi: 10.1186/s13063-017-1895-6.

Related trials for Primary Alcohol Use Disorder

Recruiting
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Evaluation of Effectiveness of the LifeSkills Training - Lombardia - Primary Shool Program ( Val3P-LST )
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The ICEC Cluster Trial: Integrated Community Engagement Collaborative for Youth Substance Use Prevention in Rural America
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A Female-Specific CBT Group for Veteran Women With Alcohol Use Disorder in VA Primary Care Settings
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Not yet recruiting
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Celia Morgan, Ph.D. principal investigator

UCL

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ketamine, Psychological Therapy and Alcohol Education in people with Primary Alcohol Use Disorder, run by University College, London at 2 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Relapse Rates (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02649231, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2021.