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Repetitive Transcranial Magnetic Stimulation (rTMS) of the Insula for Treatment of Alcohol Addiction

Primary Purpose

Alcohol Addiction

Status

Unknown status

Phase

Not Applicable

Locations

Sweden

Study Type

Interventional

Intervention

rTMS 10 Hz targeting the insula

Sham rTMS

About this trial

This is an interventional treatment trial for Alcohol Addiction focused on measuring insula, alcohol addiction, transcranial magnetic stimulation

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age 18 - 65
Current Diagnostic and Statistical Manual (DSM-IV-TR) diagnosis of alcohol dependence
Alcohol use in the past month
Right handed (self-report)
If female, negative urine pregnancy test
If female, must either agree to practice an effective birth control method; have a partner with a vasectomy; agree to abstinence from intercourse; be surgically sterile or postmenopausal for at least one year

Exclusion Criteria:

Currently pregnant or breastfeeding
More than mild cognitive impairment, as determined by a score on the Mini Mental State Examination (MMSE) <24.
Current DSM-IV diagnosis of schizophrenia, bipolar disorder, or other psychotic disorder
Use in the past 4 weeks of any medication or illicit drug listed as being associated with "a strong potential hazard for application of rTMS due to their significant seizure threshold lowering potential" by the international consensus guidelines for delivery of TMS [104], as self-reported, or detected using urine toxicology screening
Any history of clinically significant neurological disorders, including organic brain disease, epilepsy, stroke, brain lesions, multiple sclerosis, previous neurosurgery or personal history of head trauma that resulted in loss of consciousness for > 5 minutes and retrograde amnesia for > 30 minutes (self-reported history).
Any history of seizures other than febrile childhood seizures (self-reported history)
Signs of increased intracranial pressure as determined by the structural MRI-scan
Clinically significant hearing impairment or tinnitus
Presence of ferromagnetic objects in the body that are contraindicated for MRI of the head (pacemakers or other implanted electrical devices, brain stimulators, some types of dental implants, aneurysm clips, metallic prostheses, permanent eyeliner, implanted delivery pump, or shrapnel fragments) or fear of enclosed spaces. Eligibility will be determined by the "MRI Safety Screening Questionnaire" (see Appendix 1) and verified, if necessary, by a radiology consultant.
Cannot recline comfortably flat on his/her back for up to 2 hours in the MRI scanner.
Any psychiatric, medical or social condition whether or not listed above, due to which, in the judgment of the investigators and after any consults if indicated, participation in the study is not in the best interest of the patient.

Sites / Locations

Linkoping UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

rTMS 10 Hz

rTMS Sham

Arm Description

Deep Repetitive Transcranial Magnetic Stimulation (rTMS, 10 Hz) of the insula ,15 stimulation sessions (1 daily, 5 days / week).

Sham Repetitive Transcranial Magnetic Stimulation (rTMS, Sham),15 stimulation sessions (1 daily, 5 days / week).

Outcomes

Primary Outcome Measures

Heavy Drinking

Reduction in heavy alcohol use during the outpatient follow-up phase (%heavy drinking days) measured by standard Time-Line Follow-Back methodology

Insula activity

Insula activity (%signal change, as measured by fMRI BOLD), during a task known to be associated with insula responses, risky decision making

Secondary Outcome Measures

BOLD responses in a battery of standard fMRI tasks that probe processing of alcohol-associated cues, reward function, and emotional responses.

Alterations in resting-state connectivity of the insula with other nodes in the putative Salience Network (SN), executive control network (ECN) and the default-mode network (DMN) by rTMS.

Objective biomarkers of alcohol use

Gamma-glutamyl transferase (GGT); carbohydrate deficient transferrin (CDT); ethyl glucuronide (EtG) in urine and hair.

Alcohol craving and psychiatric symptoms

Measured by the Penn Alcohol Craving Scale (PACS), mood and anxiety symptoms, as measured using the respective subscales of the Comprehensive Psychiatric Rating Scale (CPRS) and Clinical Global Impression (CGI).

Smoking

Measured by urine cotinine / creatinine ratios.

Full Information

NCT ID

NCT02643264

First Posted

December 21, 2015

Last Updated

December 28, 2015

Sponsor

Linkoeping University

1. Study Identification

Unique Protocol Identification Number

NCT02643264

Brief Title

Repetitive Transcranial Magnetic Stimulation (rTMS) of the Insula for Treatment of Alcohol Addiction

Official Title

Repetitive Transcranial Magnetic Stimulation (rTMS) of the Insula for Treatment of Alcohol Addiction

Study Type

Interventional

2. Study Status

Record Verification Date

December 2015

Overall Recruitment Status

Unknown status

Study Start Date

November 2015 (undefined)

Primary Completion Date

December 2017 (Anticipated)

Study Completion Date

December 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Linkoeping University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) targeting the insula on alcohol use and neural responses in alcohol-dependent patients.

Detailed Description

Objectives: To investigate the effects of repetitive transcranial magnetic stimulation (rTMS) targeting the insula on alcohol use and neural responses in alcohol-dependent patients. Study population: Treatment seeking alcohol dependent subjects (N=82), aged 18-65 years, who have first completed standard alcohol withdrawal treatment if needed. Design: This is a double-blind, sham-controlled randomized study, comprising three phases. Participants will be hospitalized during the first two of these, and will be outpatients during the third. During Phase 1 the study (screening; up to 14 days), participants will undergo a set of baseline assessments; this phase will conclude with consent, inclusion and randomization. During Phase 2 (treatment; appr. 3 weeks, with at least the first week being hospitalized), participants will first undergo an MRI scan to collect resting state and structural data, and will then receive one of two treatments: Active (10Hz) rTMS; or sham stimulation, both targeting the insula bilaterally. rTMS sessions will be conducted five times per week, for 3 weeks, for a total of 15 sessions. Stimulation will be with an H-coil designed to reach deeper structures such as the insula. A second MRI scan will be obtained at the end of this phase to assess changes in resting state connectivity, and to evaluate insula activity in tasks known to activate this structure. In addition, a lumbar puncture will be carried out at the end of this phase to assess possible effects on central neurotransmitter and growth factor levels, as indexed in the cerebrospinal fluid. For Phase 3 (follow-up, lasting 12 weeks), patients will be followed as outpatients for 12 weeks, with clinic visits at weeks 1, 2, 4, 8 and 12 post discharge; measures of alcohol use will be collected during this phase. Outcome measures: The co-primary outcome measures will be heavy alcohol consumption during the follow-up phase, assessed using time-line follow-back methodology; and insula BOLD functional magnetic resonance imaging (fMRI) responses during tasks known to induce insula activation. A number of secondary and exploratory measures will also be assessed, including objective biomarkers of alcohol consumption.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Alcohol Addiction

Keywords

insula, alcohol addiction, transcranial magnetic stimulation

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

84 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

rTMS 10 Hz

Arm Type

Experimental

Arm Description

Deep Repetitive Transcranial Magnetic Stimulation (rTMS, 10 Hz) of the insula ,15 stimulation sessions (1 daily, 5 days / week).

Arm Title

rTMS Sham

Arm Type

Sham Comparator

Arm Description

Sham Repetitive Transcranial Magnetic Stimulation (rTMS, Sham),15 stimulation sessions (1 daily, 5 days / week).

Intervention Type

Other

Intervention Name(s)

rTMS 10 Hz targeting the insula

Intervention Description

Participants will receive a total of 15 sessions of rTMS targeting the insula bilaterally, Stimulation will be delivered at an intensity of 120% of the motor threshold (MT), with a frequency of 10 Hz, delivered as 50 trains of 30 pulses delivered in each train of 3 seconds duration, with a 20 seconds inter-train interval, for a total of 1500 pulses delivered over app. 20 min. On the very first two sessions stimulations will be given at lower strength for adaptation, starting at 100% for the first and 110% for the second session

Intervention Type

Other

Intervention Name(s)

Sham rTMS

Intervention Description

Sham stimulation with the same regimen as active treatment

Primary Outcome Measure Information:

Title

Heavy Drinking

Description

Reduction in heavy alcohol use during the outpatient follow-up phase (%heavy drinking days) measured by standard Time-Line Follow-Back methodology

Time Frame

12 weeks follow-up from treatment completion

Title

Insula activity

Description

Insula activity (%signal change, as measured by fMRI BOLD), during a task known to be associated with insula responses, risky decision making

Time Frame

Within 5 days of treatment completion

Secondary Outcome Measure Information:

Title

BOLD responses in a battery of standard fMRI tasks that probe processing of alcohol-associated cues, reward function, and emotional responses.

Time Frame

Within 5 days after the last TMS session

Title

Alterations in resting-state connectivity of the insula with other nodes in the putative Salience Network (SN), executive control network (ECN) and the default-mode network (DMN) by rTMS.

Time Frame

Within 5 days after the last TMS session

Title

Objective biomarkers of alcohol use

Description

Gamma-glutamyl transferase (GGT); carbohydrate deficient transferrin (CDT); ethyl glucuronide (EtG) in urine and hair.

Time Frame

12 weeks follow-up from treatment completion

Title

Alcohol craving and psychiatric symptoms

Description

Time Frame

12 weeks follow-up from treatment completion

Title

Smoking

Description

Measured by urine cotinine / creatinine ratios.

Time Frame

12 weeks follow-up from treatment completion

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age 18 - 65 Current Diagnostic and Statistical Manual (DSM-IV-TR) diagnosis of alcohol dependence Alcohol use in the past month Right handed (self-report) If female, negative urine pregnancy test If female, must either agree to practice an effective birth control method; have a partner with a vasectomy; agree to abstinence from intercourse; be surgically sterile or postmenopausal for at least one year Exclusion Criteria: Currently pregnant or breastfeeding More than mild cognitive impairment, as determined by a score on the Mini Mental State Examination (MMSE) <24. Current DSM-IV diagnosis of schizophrenia, bipolar disorder, or other psychotic disorder Use in the past 4 weeks of any medication or illicit drug listed as being associated with "a strong potential hazard for application of rTMS due to their significant seizure threshold lowering potential" by the international consensus guidelines for delivery of TMS [104], as self-reported, or detected using urine toxicology screening Any history of clinically significant neurological disorders, including organic brain disease, epilepsy, stroke, brain lesions, multiple sclerosis, previous neurosurgery or personal history of head trauma that resulted in loss of consciousness for > 5 minutes and retrograde amnesia for > 30 minutes (self-reported history). Any history of seizures other than febrile childhood seizures (self-reported history) Signs of increased intracranial pressure as determined by the structural MRI-scan Clinically significant hearing impairment or tinnitus Presence of ferromagnetic objects in the body that are contraindicated for MRI of the head (pacemakers or other implanted electrical devices, brain stimulators, some types of dental implants, aneurysm clips, metallic prostheses, permanent eyeliner, implanted delivery pump, or shrapnel fragments) or fear of enclosed spaces. Eligibility will be determined by the "MRI Safety Screening Questionnaire" (see Appendix 1) and verified, if necessary, by a radiology consultant. Cannot recline comfortably flat on his/her back for up to 2 hours in the MRI scanner. Any psychiatric, medical or social condition whether or not listed above, due to which, in the judgment of the investigators and after any consults if indicated, participation in the study is not in the best interest of the patient.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Markus A Heilig, MD, PhD

Phone

+46 13286626

markus.heilig@liu.se

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Markus A Heilig, MD PhD

Organizational Affiliation

Linkoping University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Linkoping University

City

Linkoping

ZIP/Postal Code

581 85

Country

Sweden

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Asa Axén, Nurse

Phone

+46 13282947

asa.axen@liu.se

12. IPD Sharing Statement

Plan to Share IPD

Yes

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Repetitive Transcranial Magnetic Stimulation (rTMS) of the Insula for Treatment of Alcohol Addiction

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