Clinical trial NCT03804619: Accelerated Intermittent Theta-Burst Stimulation for Opiate Use Disorder
Official title: Accelerated Intermittent Theta-Burst Stimulation for Opiate Use Disorder
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Opiate Dependence
Suicidal Ideation
Depression
Opioid Use
Opioid-Related Disorders
Opioid-use Disorder
Major Depressive Disorder
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2019-01-15
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open label, two-site randomized trial
Primary purpose: TREATMENT

Brief summary: This study aims to examine whether multiple spaced sessions of intermittent theta-burst transcranial magnetic stimulation (iTBS) induce anti-depressant responses and reduce opiate cravings in adults with opiate use disorder (OUD). Additionally, we hope to identify whether the effectiveness of iTBS is related to changes in functional connectivity between particular brain areas.

Detailed description: The proposed study aims to investigate the effectiveness of aiTBS applied to either the L-DLPFC or the ACC for reducing SI in individuals with OUD and identify neural functional connectivity changes underlying treatment response. 30 individuals with OUD who endorse suicidal ideation will be recruited. The accelerated iTBS treatment will involve 10 daily sessions of iTBS. Stimulation will be delivered to either the ACC or the L-DLPFC for 5 consecutive days. Suicidal ideation, depressive symptoms and opiate misuse will be measured before and after the 5-day stimulation course. Functional magnetic resonance imaging (fMRI) scans will also be carried out before and after stimulation to examine aiTBS-induced changes in neural functional connectivity. Changes in suicidal ideation, depressive symptoms and opiate misuse will be measured using both clinician-rated and self-report assessments.

Eligibility criteria: Inclusion Criteria:

1. Over 18 at the time of screening
2. Able to read, understand, and provide written, dated informed consent prior to screening. Participants will be deemed likely to comply with study protocol and communicate with study personnel about adverse events and other clinically important information.
3. Diagnosed with Opiate Use Disorder, according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders.
4. Endorse suicidal ideation (score \>2 on the SSI-C).
5. Not in a current state of mania or psychosis (Young Mania Rating Scale)
6. In good general health, as ascertained by medical history.
7. If female, a status of non-childbearing potential or use of an acceptable form of birth control per the following specific criteria:, a. Non-childbearing potential (e.g., physiologically incapable of becoming pregnant, i.e., permanently sterilized (status post hysterectomy, bilateral tubal ligation), or is post-menopausal with her last menses at least one year prior to screening); or, b. Childbearing potential, and meets the following criteria. Childbearing potential, including women using any form of hormonal birth control, on hormone replacement therapy started prior to 12 months of amenorrhea, using an intrauterine device (IUD), having a monogamous relationship with a partner who has had a vasectomy, or is sexually abstinent. ii. Negative urinary pregnancy test at screening, confirmed by a negative urinary pregnancy test at randomization prior to receiving study treatment. iii. Willing and able to continuously use one of the following methods of birth control during the course of the study, defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly: implants, injectable or patch hormonal contraception, oral contraceptives, IUD, double-barrier contraception, sexual abstinence. The form of birth control will be documented at screening and baseline.
8. Clear urine drugs test
9. Registered with a psychiatrist
10. On stable psychotropic medication or psychotherapy for at least 6 weeks prior to the study with plans to continue throughout study enrollment.
11. Failed at least one anti-depressant trial (\>/=6 week duration at an effective dose)
12. Ability to tolerate clinical study procedures.
13. No contraindications for TMS or MRI

Exclusion Criteria:

1. Any abnormalities indicated on the MRI e.g. structural neurological condition, more subcortical lesions than would be expected for age, stroke effecting stimulated area or connected areas or any other clinically significant abnormality that might affect safety, study participation, or confound interpretation of study results.
2. Metal implant in brain (e.g. deep brain stimulation), cardiac pacemaker, or cochlear
3. History of epilepsy/ seizures (including history of withdrawal/ provoked seizures)
4. Shrapnel or any ferromagnetic item in the head.
5. Pregnancy
6. Autism Spectrum disorder
7. Any current or past history of any physical condition which in the investigator's opinion might put the subject at risk or interfere with study results interpretation.
8. Active substance use (\<1 week) or intoxication verified by toxicology screen--of cocaine, amphetamines, benzodiazepines
9. Cognitive impairment (including dementia)
10. Current severe insomnia (must sleep a minimum of 5 hours the night before stimulation)
11. Current mania
12. Current unmanageable psychosis
13. Showing symptoms of withdrawal from alcohol or benzodiazepines
14. IQ\<70
15. Movement disorder
16. Any other indication the PI feels would comprise data.
17. Motor threshold value which does not enable treatment

Primary outcomes:
measure: Change in Beck Scale for Suicidal Ideation (SSI) score
timeFrame: After all stimulation sessions have been completed (approximately 48 hours after the final session)
Secondary outcomes:
measure: Change in Columbia Suicide Severity Scale (C-SSRS) score
timeFrame: After all stimulation sessions have been completed (approximately 48 hours after the final session)
measure: Change in Obsessive compulsive drug-use scale (OCDUS) score
timeFrame: After all stimulation sessions have been completed (approximately 48 hours after the final session)
measure: Change in Montgomery Asberg Depression Rating Scale (MADRS) score
timeFrame: After all stimulation sessions have been completed (approximately 48 hours after the final session)
measure: Change in Beck Depression Inventory II (BDI-II) score
timeFrame: After all stimulation sessions have been completed (approximately 48 hours after the final session)
measure: Change in resting-state functional connectivity.
timeFrame: After all stimulation sessions have been completed (approximately 48 hours after the final session)
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University
state: California
Study officials:
affiliation: Stanford University
name: Gregory Sahlem, MD
role: PRINCIPAL_INVESTIGATOR
References: