Alcohol AddictionNCT02643264
Repetitive Transcranial Magnetic Stimulation (rTMS) of the Insula for Treatment of Alcohol Addiction
A study testing rTMS 10 Hz targeting the insula in people with Alcohol Addiction, run by Linkoeping University at 1 site in Sweden.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Alcohol Addiction
- What is being tested?
- rTMS 10 Hz targeting the insula
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 84 participants
- Where
- 1 siteSweden
- Study dates
- Nov 2015to Dec 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
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- 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.
Trial locations and contacts
1 site in 1 country.
Sweden1 site, 1 recruiting
- Recruiting
Linkoping University
Linköping, 581 85
Asa Axén, Nurse, +46 13282947, asa.axen@liu.se
About this study
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.
Read the 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.
- Conditions
- Alcohol Addiction
- Being tested
- rTMS 10 Hz targeting the insula, Sham rTMS
- Keywords
- insula, alcohol addiction, transcranial magnetic stimulation
- Medical subject headings
- Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rTMS 10 Hz targeting the insulaOther
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
Sham rTMSOther
Sham stimulation with the same regimen as active treatment
| Study group | Role | What they receive |
|---|---|---|
| rTMS 10 Hz | Experimental | Deep Repetitive Transcranial Magnetic Stimulation (rTMS, 10 Hz) of the insula ,15 stimulation sessions (1 daily, 5 days / week). Receives: Other: rTMS 10 Hz targeting the insula |
| rTMS Sham | Sham comparator | Sham Repetitive Transcranial Magnetic Stimulation (rTMS, Sham),15 stimulation sessions (1 daily, 5 days / week). Receives: Other: Sham rTMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Heavy Drinking
Reduction in heavy alcohol use during the outpatient follow-up phase (%heavy drinking days) measured by standard Time-Line Follow-Back methodology
Measured: 12 weeks follow-up from treatment completion
Insula activity
Insula activity (%signal change, as measured by fMRI BOLD), during a task known to be associated with insula responses, risky decision making
Measured: Within 5 days of treatment completion
Secondary outcomes (5)
BOLD responses in a battery of standard fMRI tasks that probe processing of alcohol-associated cues, reward function, and emotional responses.
Measured: Within 5 days after the last TMS session
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.
Measured: Within 5 days after the last TMS session
Objective biomarkers of alcohol use
Gamma-glutamyl transferase (GGT); carbohydrate deficient transferrin (CDT); ethyl glucuronide (EtG) in urine and hair.
Measured: 12 weeks follow-up from treatment completion
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).
Measured: 12 weeks follow-up from treatment completion
Smoking
Measured by urine cotinine / creatinine ratios.
Measured: 12 weeks follow-up from treatment completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Dec 2015 (estimated)
- Study startNov 2015
- Primary completionDec 2017 (estimated)
- Study completionDec 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alcohol AddictionStudies of the same condition, open and under way.
- More trials run by Linkoeping UniversityThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 84 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Linkoeping University
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Markus Heilig, Linkoeping University
- Investigators
- Markus A Heilig, MD PhD, Principal investigator, Linkoeping University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02643264
- Sponsor's protocol ID
- LIU2015/130-31
- Status last verified
- Dec 2015
- First submitted
- 21 Dec 2015
- Last updated
- 31 Dec 2015
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Repetitive Transcranial Magnetic Stimulation (rTMS) of the Insula for Treatment of Alcohol Addiction
- ClinicalTrials.gov ID
- NCT02643264
- Acronym / sponsor ID
- LIU2015/130-31
- Conditions
- Alcohol Addiction
- Keywords
- insula, alcohol addiction, transcranial magnetic stimulation
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 84 participants (estimated)
- Lead sponsor
- Linkoeping UniversityOther government
- Study start
- Nov 2015
- Primary completion
- Dec 2017 (estimated)
- Study completion
- Dec 2017 (estimated)
- First posted
- 31 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| rTMS 10 Hz | Experimental | Other: rTMS 10 Hz targeting the insulaDeep Repetitive Transcranial Magnetic Stimulation (rTMS, 10 Hz) of the insula ,15 stimulation sessions (1 daily, 5 days / week). |
| rTMS Sham | Sham comparator | Other: Sham rTMSSham Repetitive Transcranial Magnetic Stimulation (rTMS, Sham),15 stimulation sessions (1 daily, 5 days / week). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (11 listed)
- 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).
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 |
|---|---|---|
| rTMS 10 Hz targeting the insulaParticipants 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 | Other | rTMS 10 Hz |
| Sham rTMSSham stimulation with the same regimen as active treatment | Other | rTMS Sham |
Primary outcome
Heavy Drinking
Time frame: 12 weeks follow-up from treatment completion
Reduction in heavy alcohol use during the outpatient follow-up phase (%heavy drinking days) measured by standard Time-Line Follow-Back methodology
Insula activity
Time frame: Within 5 days of treatment completion
Insula activity (%signal change, as measured by fMRI BOLD), during a task known to be associated with insula responses, risky decision making
5 secondary outcomes
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
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
Objective biomarkers of alcohol use
Time frame: 12 weeks follow-up from treatment completion
Alcohol craving and psychiatric symptoms
Time frame: 12 weeks follow-up from treatment completion
Smoking
Time frame: 12 weeks follow-up from treatment completion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Dec 2015.
- Individual participant dataSharing planned: Yes
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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.
Markus A Heilig, MD PhD principal investigator
Linkoeping University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing rTMS 10 Hz targeting the insula in people with Alcohol Addiction, run by Linkoeping University at 1 site in Sweden.
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 6 inclusion and 11 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: status not confirmed, as of the sponsor's last update on 31 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Markus A Heilig, MD, PhD (+46 13286626, markus.heilig@liu.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Heavy Drinking (time frame: 12 weeks follow-up from treatment completion). 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?
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 31 Dec 2015.