Evaluation of Bilateral HF-rTMS on Abstinence in Alcohol Use Disorder Patients With Executive Dysfunction

Alcohol Withdrawal Clinical Trial

— STIM-ALC  

Official title:

Evaluation of Bilateral HF-rTMS Over DLPFC in add-on to Usual Treatment on Abstinence in Alcohol Use Disorder Patients With Executive Dysfunction After Withdrawal

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04997330
• Other study ID #: APHP180582
• Secondary ID: 2020-A00548-31
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 2021
• Est. completion date: July 2023

Study information

• Verified date: March 2021
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Fanny LEVY, Docteur
• Phone: 01.42.16.28.94
• Email: fanny.levy[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

High frequency repetitive transcranial magnetic stimulation (HF-rTMS) over dorsolateral prefrontal cortex (DLPFC) could correct defective executive functions over the hyperactive reward circuit through the meso-fronto-limbic connections. The restored cortical inhibitory control over compulsive alcohol use, could improve abstinence after withdrawal. The goal of this study is to evaluate the efficacy of HF-rTMS over DLPFC in AUD patients with executive dysfunction after withdrawal.

Description:

PARTICIPANTS:

Participants with AUD (moderate to mild according to Alcohol Dependance Scale) with executive dysfunctions will be randomized.

DESIGN:

This study is a multicenter pilot double blind randomized controlled trial. After at least seven days of alcohol residential detoxification, executive dysfunctions's participants will be tested. 64 of them with executive dysfunctions will be randomized either in the active rTMS group or in the sham rTMS group. TMS will be performed during hospitalisation over 10 days. rTMS are proposed as an add on to the usual treatment.

INTERVENTION:

20 rTMS (twice a day) will be performed 10 consecutive working days. The target of the rTMS will be the DLPFC (left side in the morning, right side in the afternoon). During each rTMS sessions (active and sham), alcohol related pictures from the Geneva Appetitive alcohol Pictures will be presented.In the active arm, rTMS will be performed with high frequency (20hz, 1500 pulses per session, 110% of motor threshold).In the control group, sham rTMS will be performed.

Participants will be follow up to three months after the end of rTMS treatment.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 95
• Est. completion date: July 2023
• Est. primary completion date: May 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Age between 18-75 years

• Alcohol use disorder according to DSM 5, moderate to mild according to ADS

• Residential stay for alcohol detoxofication

Exclusion Criteria:

• Cognitive deficits defined by MoCA <25 (Montreal Cognitive Assessment) performed at least 7days after alcohol detoxification and after at least 12 hours after benzodiazepine cessation

• History of cerebral stroke

• DSM-5 substance use disorders other than nicotine and alcohol

• Contraindication for rTMS :

• Pregnancy

• History of epilepsy or seizure

• Cochlear implants

• Cardiac pacemaker or intracardiac lines, or metal in the body

• Clinical history of complicated withdrawal symptoms

• History of severe head trauma followed by loss of consciousness

• Actual major depressive episode, schizophrenia according to the MINI (Mini International Neuropsychiatric Interview)

• Breastfeeding women

• Actual or history of organic failure including cirrhosis

• Absence of health insurance; or patient with AME

• Legal protection (curatorship or tutorship)

• Deprive of freedom or security measure

• No adequate mastering of the French language or no ability to consent

• Major socio-economic problem: homelessness

• No written informed consent

• Participation in another interventional study

Secondary inclusion criteria (before randomization):

• Abnormal executive function defined as at least 3 impaired measurements among 19 measurements of 7 tests (Stroop test, Wisconsin test; Trail making test, verbal fluency, 6 elements, Brixton test, Dual task Baddeley test) from the Greffex battery. Each measure will be considered as impaired if it is below 1.65 SD. The procedure and the measurement are standardized. The neuropsychological evaluation will be performed at least seven days after alcohol detoxification and after at least 12 hours after benzodiazepine cessation.

Related Conditions & MeSH terms

• Alcohol Withdrawal
• Alcoholism

Intervention

Device:
• Active rTMS
Bilateral high frequency (20Hz) rTMS will be delivered (over dorsolateral prefrontal cortex), at two daily sessions (left side on the morning and right side on the afternoon), 10 consecutive days on working day, 1500 pulses/session, 110% of motor threshold determined, 30 trains, 50 pulses per train and 15s inter train. A session will typically last around 10 minutes. Alcohol cues consisted of a selection of 60 alcohol-related pictures (beverage, drinking-related behaviors, alcohol-related cues) from the Geneva Appetitive alcohol Pictures will be presented during each rTMS session.
• Sham rTMS
Sham rTMS will be delivered (over dorsolateral prefrontal cortex) , at two daily sessions (left side on the morning and right side on the afternoon), 10 consecutive working days. A session will typically last around 10 minutes. Alcohol cues consisted of a selection of 60 alcohol-related pictures (beverage, drinking-related behaviors, alcohol-related cues) from the Geneva Appetitive alcohol Pictures will be presented during each rTMS session.

Locations

Country	Name	City	State
France	Hôpital Universitaire Pitié-Salpêtrière	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of participants with continuous complete alcohol abstinence	Percentage of patients with continuous complete abstinence up to one month after the end of the rTMS treatment.; The abstinence will be assessed using the Alcohol-Time Line Follow Back tool (TLFB). The Alcohol TLFB is a descriptive questionnaire, using a calendar, participants will retrospectively record at M1 the number of days they drank over the 30 days following the end of the rTMS treatment. Continuous complete abstinence will be defined as no day with alcohol consumption over the 30 days.	1 month after the end of rTMS sessions
Secondary	Percentage of participants with alcohol continuous complete abstinence	Percentage of patients with continuous complete abstinence up to 3 months after the end of the rTMS treatment.; The abstinence will be assessed using the Alcohol-TLFB at M1, M2, M3. Continuous complete abstinence will be defined as no day with alcohol consumption over the 90 days.	3 months after the end of rTMS sessions
Secondary	Number of cumulative abstinence days	Alcohol consumption measured by the number of cumulative abstinence days up to 1 month after the end of the rTMS treatment. The number of cumulative abstinence days will be assessed using (TLFB) at M1 and will be calculated by summing the total number of days when no alcohol was consumed over the 30 days.	1 month after the end of rTMS sessions
Secondary	Number of cumulative abstinence days	Alcohol consumption measured by the number of cumulative abstinence days up to 3 months after the end of the rTMS treatment. The number of cumulative abstinence days will be assessed using (TLFB) at M1, M2, M3 and will be calculated by summing the total number of days when no alcohol was consumed over the 90 days.	3 months after the end of rTMS sessions
Secondary	Time until the first heavy drinking days (HDD)	Time until the first heavy drinking days (HDD) up to 3 months. The time, in days, until the first HDD will be assessed using (TLFB) at M1, M2, M3. HDD will be defined as more than 50 (men) or 40 (women) g/day.	3 months after the end of rTMS sessions
Secondary	Number of heavy drinking days (HDD)	Number of heavy drinking days (HDD) up to 1 month. Number of heavy drinking days HDD will be assessed using (TLFB) at M1 and will be calculated by summing the total number of days with HDD over the 30 days. HDD will be defined as more than 50 (men) or 40 (women) g/day.	1 month after the end of rTMS sessions
Secondary	Number of heavy drinking days (HDD)	Number of heavy drinking days (HDD) up to 3 months. Number of heavy drinking days HDD will be assessed using (TLFB) at M1, M2, M3 and will be calculated by summing the total number of days with HDD over the 90 days.. HDD will be defined as more than 50 (men) or 40 (women) g/day.	3 month after the end of rTMS sessions
Secondary	Time to relapse	The time to relapse, in days, will be assessed using (TLFB) at M1, M2, M3. Relapse will be defined as a day with a consumption equal or higher than 50% of initial intake.	3 months after the end of rTMS sessions
Secondary	Alcohol dependence severity assessed by the Alcohol Dependence Scale (ADS)	Alcohol dependence severity will be evaluated with the Alcohol Dependence Scale (ADS). The ADS is a self-administrated 25-items questionnaire (requiring 5 minutes) assessing alcohol withdrawal symptoms, impaired control over drinking, awareness of compulsive drink, increased tolerance and salience of drink-seeking behavior. ADS is initially used to assess a past 12-month period, its instructions can be modified for different time-frame. The ADS will be assessed on previous 4 weeks. This scale is scored out of 47, higher scores are considered worse.	1 month after the end of rTMS sessions
Secondary	Alcohol dependence severity assessed by the Alcohol Dependence Scale (ADS)	Alcohol dependence severity will be evaluated with the Alcohol Dependence Scale (ADS). The ADS is a self-administrated 25-items questionnaire (requiring 5 minutes) assessing alcohol withdrawal symptoms, impaired control over drinking, awareness of compulsive drink, increased tolerance and salience of drink-seeking behavior. ADS is initially used to assess a past 12-month period, its instructions can be modified for different time-frame. The ADS will be assessed on previous 4 weeks. This scale is scored out of 47, higher scores are considered worse.	3 months after the end of rTMS sessions
Secondary	Alcohol cue induced craving using the Cue induced Obsessive Compulsive Drinking Scale (OCDS)	Evaluated by Cue induced Obsessive Compulsive Drinking Scale (OCDS). Cue induced OCDS will be measured after alcohol cues viewing. French version of OCDS is a self-administrated 14-items instrument assessing obsessive and compulsive characteristics of drinking-related thoughts, urge to drink or craving, and ability to resist those thoughts and urges. This scale is scored out of 56, higher scores are considered worse. Alcohol cues consisted of a selection of 60 alcohol-related pictures (beverage, drinking-related behaviors, alcohol-related cues) from the Geneva Appetitive alcohol Pictures . The same diaporama will be used for all visits in all centers.	At the last day of rTMS sessions
Secondary	Alcohol cue induced craving using the Cue induced Obsessive Compulsive Drinking Scale (OCDS)	Evaluated by Cue induced Obsessive Compulsive Drinking Scale (OCDS). Cue induced OCDS will be measured after alcohol cues viewing. French version of OCDS is a self-administrated 14-items instrument assessing obsessive and compulsive characteristics of drinking-related thoughts, urge to drink or craving, and ability to resist those thoughts and urges. This scale is scored out of 56, higher scores are considered worse. Alcohol cues consisted of a selection of 60 alcohol-related pictures (beverage, drinking-related behaviors, alcohol-related cues) from the Geneva Appetitive alcohol Pictures . The same diaporama will be used for all visits in all centers.	at 1 month after the end of rTMS sessions
Secondary	Alcohol cue induced craving using the Cue induced Obsessive Compulsive Drinking Scale (OCDS)	Evaluated by Cue induced Obsessive Compulsive Drinking Scale (OCDS). Cue induced OCDS will be measured after alcohol cues viewing. French version of OCDS is a self-administrated 14-items instrument assessing obsessive and compulsive characteristics of drinking-related thoughts, urge to drink or craving, and ability to resist those thoughts and urges. This scale is scored out of 56, higher scores are considered worse. Alcohol cues consisted of a selection of 60 alcohol-related pictures (beverage, drinking-related behaviors, alcohol-related cues) from the Geneva Appetitive alcohol Pictures . The same diaporama will be used for all visits in all centers.	at 3 months after the end of rTMS sessions
Secondary	Change in Alcohol cue induced craving using a Visual Analogic Scale (VAS)	Change in cue induced craving Visual Analogic Scale (VAS) from baseline to the last rTMS session.; Cue induced craving VAS will be measured after alcohol cues viewing at baseline and then daily on the morning just before rTMS sessions. The VAS is scored out of 10, higher scores are considered worse. Alcohol cues will be the same as for OCDS.	From baseline to the last rTMS session after the end of rTMS sessions
Secondary	Alcohol cue induced craving using a Visual Analogic Scale (VAS)	The VAS is scored out of 10, higher scores are considered worse. Alcohol cues will be the same as for OCDS.	At 1 month after the end of rTMS sessions
Secondary	Alcohol due induced craving using a Visual Analogic Scale (VAS)	The VAS is scored out of 10, higher scores are considered worse. Alcohol cues will be the same as for OCDS.	At 3 months after the end of rTMS sessions
Secondary	Number of impaired measures on the Grefex batery (executive functions)	Executive performance will be evaluated by the number of impaired measures on the Grefex battery : Stroop test, Wisconsin Test, Trail Making Test, verbal fluency, 6 elements, Brixton test and Dual task Baddeley test. Upon these 7 tests, 19 index will be measured (number of errors, time to make the task .). Each measure will be considered as impaired if it is below 1.65 SD. Number of impaired measures will be recorded for each patient.	1 month after the end of rTMS sessions
Secondary	Stroop test	Stroop test will be performed 1 month after the end of the rTMS sessions. The stroop test assess the cognitive inhibition. Time and number of non-corrected errors will be reported for each conditions 1) denomination 2) reading 3) interference.	1 month after the end of rTMS sessions
Secondary	Trail making test	Trail making test will be performed 1 month after the end of the rTMS sessions. The trail making test assess the mental flexibility. Time and number of errors will be reported for the trail making test A and the trail making test B. For this last condition, the number of perserverations will be also reported.	1 month after the end of rTMS sessions
Secondary	Verbal fluency	Verbal fluency will be performed 1 month after the ned of the rTMS sessions. The verbal fluency assess the lexical generation ability. The number of words produced will be reported.	1 month after the end of rTMS sessions
Secondary	Wisconsin Test	Wisconsin test will be performed 1 month after the ned of the rTMS sessions. The Wisconsin test assess the ability of deduction and rules maintenance. Number of correct categories, number of errors and number of perseverations will be reported.	1 month after the end of rTMS sessions
Secondary	Brixton test	Brixton test test will be performed 1 month after the ned of the rTMS sessions. The Brixton test assess the deduction abilify of working rules. Number of errors will be reported.	1 month after the end of rTMS sessions
Secondary	6 elements	6 elements test will be performed 1 month after the ned of the rTMS sessions. The 6 elements test assess the planning and organization ability of the behavior. Ranking score will be reported.	1 month after the end of rTMS sessions
Secondary	Dual task Baddeley test	Dual task Baddeley testwill be performed 1 month after the end of the rTMS sessions. The Dual task Baddeley assess the working memory. Mu index will be reported.	1 month after the end of rTMS sessions
Secondary	Quality of life assessed by the Quality of life Scale (AQoLS)	Quality of life will be evaluated with Alcohol Quality of Life Scale (AQoLS) French version. This scale is a self-administrated 34-item questionnaire measuring health-related quality of life. The questionnaire explores 7 domains, i.e. activities, relationships, self-esteem, negative emotions, living conditions, control and sleep. The total score was obtained by summing all items, and the theoretical range was therefore 0-102; higher scores are considered better.	At 1 month after the end of rTMS sessions
Secondary	Quality of life assessed by the Quality of life Scale (AQoLS)	Quality of life will be evaluated with Alcohol Quality of Life Scale (AQoLS) French version. This scale is a self-administrated 34-item questionnaire measuring health-related quality of life. The questionnaire explores 7 domains, i.e. activities, relationships, self-esteem, negative emotions, living conditions, control and sleep. The total score was obtained by summing all items, and the theoretical range was therefore 0-102; higher scores are considered better.	At 3 months after the end of rTMS sessions
Secondary	% rTMS stimulation performed with optimal stimulation parameters	Achievement of optimal stimulation parameters will be assessed for each patient by the percentage of sessions performed with the theoretical threshold (110%).	At the end of rTMS treatment
Secondary	Percentage of rTMS sessions performed.	Treatment compliance will be assessed by the percentage of rTMS sessions performed.	At the end of rTMS treatment
Secondary	Percentage of participants experiencing sides effect	rTMS security will be assessed by the percentage of patients experiencing sides effects during the study and their nature: seizure induction, transient acute hypomania induction, syncope, transient headache, local pain, neck pain, toothache, paresthesia, transient hearing changes, other.	3 months at the end of rTMS treatment