Pre-post Evaluation of the Safety and Efficacy of Ibogaine-Magnesium Therapy in Veterans With Repeated Blast Exposure

• ClinicalTrials.gov Identifier: NCT04313712
• Recruitment Status: Active, not recruiting
• First Posted: March 18, 2020
• Last Update Posted: August 9, 2023
• Sponsor: Stanford University
• Information provided by (Responsible Party): Nolan R, Stanford University

Tracking Information

• First Submitted Date: March 16, 2020
• First Posted Date: March 18, 2020
• Last Update Posted Date: August 9, 2023
• Actual Study Start Date: November 15, 2021
• Estimated Primary Completion Date: February 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 22, 2022)

Change in score on the WHODAS 2.0 [ Time Frame: Baseline to immediate post visit. ]

The WHODAS 2.0 is a generic assessment of disability across six domains of functioning including cognition, mobility, self-care, interpersonal relationships, life activities, and community activities. The higher the score, the greater the level of self-reported disability in functioning. Scores from baseline will be compared to scores at the immediate post-treatment.

Original Primary Outcome Measures (submitted: March 16, 2020)

• Percentage change in WAIS Block Design Subtest scores [ Time Frame: Change will be assessed between baseline and immediate post visits ]
  A measure of visual-spatial and organizational processing abilities, as well as nonverbal problem-solving skills
• Percentage change in WAIS Coding Subtest scores [ Time Frame: Change will be assessed between baseline and immediate post visits ]
  A measure of visual-motor coordination, motor and mental speed
• Percentage change in WAIS Digit Span Subtest scores [ Time Frame: Change will be assessed between baseline and immediate post visits ]
  A measure of spatial perception, visual abstract processing & problem solving
• Percentage change in Trail Making Task A & B scores [ Time Frame: Change will be assessed between baseline and immediate post visits ]
  A 2 part test in which the subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy to measure visual search speed, scanning, speed of processing, mental flexibility, as well as executive functioning.
• Percentage change in Hopkins Verbal Learning Test-Revised scores [ Time Frame: Change will be assessed between baseline and immediate post visits ]
  A test of verbal learning and memory.

Current Secondary Outcome Measures (submitted: March 22, 2022)

Change in score on the WHODAS 2.0 [ Time Frame: Baseline to 1-month post visit. ]

The WHODAS 2.0 is a generic assessment of disability across six domains of functioning including cognition, mobility, self-care, interpersonal relationships, life activities, and community activities. The higher the score, the greater the level of self-reported disability in functioning. Scores from baseline will be compared to scores at 1-month post-visit.

Original Secondary Outcome Measures (submitted: March 16, 2020)

• Percent change in the Hamilton Depression Rating Scale (HAMD-21) [ Time Frame: Changes will be measured between baseline, immediate post, and one month post time points. ]
  A provider administered questionnaire used to assess remission and recovery from depression
• Percentage change in the Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Changes will be measured between baseline, immediate post, and one month post time points. ]
  A ten item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders.
• Change in the PTSD Symptom Scale Interview-5 scores [ Time Frame: Changes will be measured between the baseline and one month time points. ]
  A clinically administered questionnaire to assess the presence of PTSD (Post Traumatic Stress Disorder) according to DSM-V criteria and assess the severity of PTSD symptoms in individuals with a known trauma history.
• Change in responses to the Quality of Life Enjoyment and Satisfaction Questionnaire. [ Time Frame: Changes will be measured between the baseline, immediate post and one month time points. ]
  A self-report measure designed to enable investigators to measure the degree of enjoyment and satisfaction experienced by subjects in various areas of daily functioning.
• Changes in Cognitive Failures Questionnaire scores [ Time Frame: Changes will be measured between baseline and one month post visits ]
  A 25 item self-report questionnaire to assess the frequency with which people experienced cognitive failures, such as absent-mindedness, in everyday life
• Structural changes measured by an MRI [ Time Frame: Changes will be measured between baseline and immediate post time points ]
  Using a MRI scan of the brain to measure total gray matter and structural changes in the Ventral diencephalon, frontal lobes, and hippocampus.
• Changes in functional connectivity measured by an fMRI [ Time Frame: Changes will be measured between baseline and immediate post time points ]
  Using a fMRI to examine irregularity in the default mode network

• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: March 16, 2020)

• Percentage change in substance use measured by the Addiction Severity Index-Lite [ Time Frame: Changes will be measured between the baseline and one month post visits ]
  A semi-structured interview to assess substance use change over the past 30 days.
• Percentage change in CAPS-5 score [ Time Frame: Changes will be measured between the baseline and one month post visits ]
  A clinically administered instrument to assess PTSD symptoms and severity.
• Percentage change in disability functioning measured by the WHODAS [ Time Frame: Changes will be measured between baseline and one month post visits ]
  A 36 item self-report questionnaire to assess disability levels relating to a health condition overall and in 6 different domains: cognition, mobility, self-care, getting along with others, participation in society, and life activities
• Percentage change in the Scale of Suicidal Ideation [ Time Frame: Changes will be measured between baseline, immediate post, and one month post visits ]
  A clinician-rating scale presented in a semi-structured interview format designed to assess the intensity, pervasiveness, and characteristics of suicidal ideation in adults.
• Change in symptoms measured by the Symptom Checklist 90 Revised (SCL-90-R) [ Time Frame: Changes will be measured between baseline, immediate post, and one month post visits ]
  A 90 item self-report questionnaire to evaluate a broad range of psychological problems and symptoms of psychopathology that is also useful in measuring patient progress or treatment outcomes.
• Percentage change in the Five Facets Mindfulness Questionnaire (FFMQ) [ Time Frame: Changes will be measured between baseline, immediate post, and one month post visits ]
  A 39 item self-report questionnaire to assess the 5 facets of mindfulness.
• Percentage change in the Forms of Self-Criticising/Attacking & Self-Reassuring Scale (FSCRS) [ Time Frame: Changes will be measured between baseline, immediate post, and one month post visits ]
  A 22 item self-report instrument that measures self-criticism and self-reassurance
• Percentage change in the Becks Depression Inventory II (BDI-II) [ Time Frame: Changes will be measured between baseline, immediate post, and one month post visits ]
  A 21 item self-report criteria-referenced assessment for measuring depression severity

Descriptive Information

• Brief Title: Pre-post Evaluation of the Safety and Efficacy of Ibogaine-Magnesium Therapy in Veterans With Repeated Blast Exposure
• Official Title: A Pre-post Study Evaluating the Safety and Efficacy of Ibogaine-Magnesium Therapy in Veterans With Sequelae of Repeated Blast Exposure
• Brief Summary: A Pre-post Study Evaluating the Safety and Efficacy of Ibogaine-Magnesium Therapy in Veterans with Sequelae of Repeated Blast Exposure.

Detailed Description

Traumatic brain injury (TBI) is a leading cause of disability worldwide and is particularly common among combat veterans. Deleterious sequelae can include functional impairments and comorbid psychiatric syndromes such as posttraumatic stress disorder (PTSD), depression, and anxiety. Special Operations Forces Veterans (SOV) may be at an elevated risk for these complications, leading some to seek treatment alternatives like the oneirogen ibogaine despite limited evidence of safety or efficacy.

We will assess the safety profile of the compound by assessing unexpected or serious adverse events.

The primary outcome will be change in the World Health Organization Disability Assessment Schedule 2.0 (WHODAS) from baseline to post-treatment, with change from baseline to the one-month follow-up a secondary outcome.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: Veterans with a history of head trauma, combat or blast exposure that have arranged for ibogaine-magnesium therapy in other countries.

Condition

• Blast or Combat Exposure
• Head Injury Trauma

Intervention

Drug: ibogaine with magnesium treatment

Participants will receive magnesium sulfate intravenously and ibogaine orally.

Study Groups/Cohorts

Participants

All study participants will be observed before and after they receive ibogaine-magnesium therapy.

Intervention: Drug: ibogaine with magnesium treatment

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: March 16, 2020): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 2024
• Estimated Primary Completion Date: February 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Male or female veteran, 18 to 70 years of age, inclusive, at screen.
2. Able to read, understand, and provide written, dated informed consent prior to screening. Participants will be deemed likely to comply with the study protocol and communicate with study personnel about adverse events and other clinically important information.
3. Has a history of head trauma, combat or blast exposure.
4. Scheduled themselves for ibogaine-magnesium therapy at Nouvelle Vie in Mexico.
5. Participants must be willing and able to travel to Stanford University before and after ibogaine-magnesium therapy.
6. Capable of getting an MRI scan.
7. Willing to be video recorded during the consenting process. (to be stored on a secure server, no PHI associated with video recordings)
8. Body mass index between 17-35kg/m2.

9. If female, a status of non-childbearing potential or use of an acceptable form of birth control per the following specific criteria:

   1. 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
   2. Childbearing potential, and meets the following criteria:

   i. 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.

10. Participants must be US citizens.

Exclusion Criteria:

1. Female of childbearing potential who is not willing to use one of the specified forms of birth control during the study.
2. Female that is pregnant or breastfeeding.
3. Claustrophobic.
4. History of a neurological disorder (i.e. Parkinson's, epilepsy, dementia, etc.) excluding sequelae of traumatic injury.
5. In the judgment of the investigator, the subject is at significant risk for suicidal behavior during the course of their participation in the study.
6. History of schizophrenia or schizoaffective disorders, or any history of psychotic symptoms.
7. Has a clinically significant abnormality on the screening physical examination that might affect safety, study participation, or confound interpretation of study results.
8. Participation in any clinical trial with an investigational drug or device within the past month or concurrent to study participation.
9. 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.
10. Any history of cardiovascular problems.
11. Any history of liver or kidney problems.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04313712
• Other Study ID Numbers: 54095
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Nolan R, Stanford University
• Original Responsible Party: Same as current
• Current Study Sponsor: Stanford University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Nolan Williams, MD; Stanford University

• PRS Account: Stanford University
• Verification Date: August 2023