Evaluation of Bilateral HF-rTMS on Abstinence in Alcohol Use Disorder Patients With Executive Dysfunction (STIM-ALC)
2021年8月27日 更新者：Assistance Publique - Hôpitaux de Paris
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
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.
調査の概要
詳細な説明
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.
研究の種類
介入
入学 (予想される)
95
段階
- 適用できない
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究連絡先
- 名前：Fanny LEVY, Docteur
- 電話番号：01.42.16.28.94
- メール：fanny.levy@aphp.fr
研究連絡先のバックアップ
- 名前：Romain ICICK, Docteur
- 電話番号：01 40 05 48 69
- メール：romain.icick@aphp.fr
研究場所
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-
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Paris、フランス、75013
- Hôpital Universitaire Pitié-Salpêtrière
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コンタクト：
- Anne Radenne
- 電話番号：01 42 16 16 99
- メール：anne.radenne@aphp.fr
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年～75年 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
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.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：トリプル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：Active rTMS
Bilateral high frequency (20Hz) Repetitive Transcranial Magnetic Stimulation (rTMS) over DLPFC
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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.
他の名前：
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プラセボコンパレーター：Sham rTMS
Sham bilateral high frequency (20Hz) Repetitive Transcranial Magnetic Stimulation (rTMS) over DLPFC
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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.
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Percentage of participants with continuous complete alcohol abstinence
時間枠：1 month after the end of rTMS sessions
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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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Percentage of participants with alcohol continuous complete abstinence
時間枠：3 months after the end of rTMS sessions
|
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
|
|
Number of cumulative abstinence days
時間枠：1 month after the end of rTMS sessions
|
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
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Number of cumulative abstinence days
時間枠：3 months after the end of rTMS sessions
|
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.
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3 months after the end of rTMS sessions
|
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Time until the first heavy drinking days (HDD)
時間枠：3 months after the end of rTMS sessions
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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
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Number of heavy drinking days (HDD)
時間枠：1 month after the end of rTMS sessions
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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.
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1 month after the end of rTMS sessions
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Number of heavy drinking days (HDD)
時間枠：3 month after the end of rTMS sessions
|
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.
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3 month after the end of rTMS sessions
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Time to relapse
時間枠：3 months after the end of rTMS sessions
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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.
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3 months after the end of rTMS sessions
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Alcohol dependence severity assessed by the Alcohol Dependence Scale (ADS)
時間枠：1 month after the end of rTMS sessions
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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
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Alcohol dependence severity assessed by the Alcohol Dependence Scale (ADS)
時間枠：3 months after the end of rTMS sessions
|
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
|
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Alcohol cue induced craving using the Cue induced Obsessive Compulsive Drinking Scale (OCDS)
時間枠：At the last day of rTMS sessions
|
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
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Alcohol cue induced craving using the Cue induced Obsessive Compulsive Drinking Scale (OCDS)
時間枠：at 1 month after the end of rTMS sessions
|
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
|
|
Alcohol cue induced craving using the Cue induced Obsessive Compulsive Drinking Scale (OCDS)
時間枠：at 3 months after the end of rTMS sessions
|
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
|
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Change in Alcohol cue induced craving using a Visual Analogic Scale (VAS)
時間枠：From baseline to the last rTMS session after the end of rTMS sessions
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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
|
|
Alcohol cue induced craving using a Visual Analogic Scale (VAS)
時間枠：At 1 month after the end of rTMS sessions
|
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
|
|
Alcohol due induced craving using a Visual Analogic Scale (VAS)
時間枠：At 3 months after the end of rTMS sessions
|
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
|
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Number of impaired measures on the Grefex batery (executive functions)
時間枠：1 month after the end of rTMS sessions
|
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
|
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Stroop test
時間枠：1 month after the end of rTMS sessions
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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.
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1 month after the end of rTMS sessions
|
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Trail making test
時間枠：1 month after the end of rTMS sessions
|
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
|
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Verbal fluency
時間枠：1 month after the end of rTMS sessions
|
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
|
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Wisconsin Test
時間枠：1 month after the end of rTMS sessions
|
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
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Brixton test
時間枠：1 month after the end of rTMS sessions
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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
|
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6 elements
時間枠：1 month after the end of rTMS sessions
|
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
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Dual task Baddeley test
時間枠：1 month after the end of rTMS sessions
|
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
|
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Quality of life assessed by the Quality of life Scale (AQoLS)
時間枠：At 1 month after the end of rTMS sessions
|
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
|
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Quality of life assessed by the Quality of life Scale (AQoLS)
時間枠：At 3 months after the end of rTMS sessions
|
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
|
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% rTMS stimulation performed with optimal stimulation parameters
時間枠：At the end of rTMS treatment
|
Achievement of optimal stimulation parameters will be assessed for each patient by the percentage of sessions performed with the theoretical threshold (110%).
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At the end of rTMS treatment
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Percentage of rTMS sessions performed.
時間枠：At the end of rTMS treatment
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Treatment compliance will be assessed by the percentage of rTMS sessions performed.
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At the end of rTMS treatment
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Percentage of participants experiencing sides effect
時間枠：3 months at the end of rTMS treatment
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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.
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3 months at the end of rTMS treatment
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
捜査官
- 主任研究者：Fanny LEVY, Docteur、Assistance Publique - Hôpitaux de Paris
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (予想される)
2021年9月1日
一次修了 (予想される)
2023年5月1日
研究の完了 (予想される)
2023年7月1日
試験登録日
最初に提出
2021年7月31日
QC基準を満たした最初の提出物
2021年7月31日
最初の投稿 (実際)
2021年8月9日
学習記録の更新
投稿された最後の更新 (実際)
2021年8月30日
QC基準を満たした最後の更新が送信されました
2021年8月27日
最終確認日
2021年3月1日
詳しくは
本研究に関する用語
その他の研究ID番号
- APHP180582
- 2020-A00548-31 (その他の識別子：N° IDRCB)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
はい
IPD プランの説明
Data are available upon reasonable request. The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients.
Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.
IPD 共有時間枠
Beginning 3 months and ending 3 years following article publication.
Requests out of these time frame can also be submitted to the sponsor
IPD 共有アクセス基準
Researchers who provide a methodologically sound proposal
IPD 共有サポート情報タイプ
- STUDY_PROTOCOL
- SAP
- ICF
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
いいえ
米国FDA規制機器製品の研究
いいえ
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