Ibogaine in the Treatment of Alcoholism: a Randomized, Double-blind, Placebo-controlled, Escalating-dose, Phase 2 Trial

Study Overview
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Brief Summary
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Approximately 5% of the world's adult population has some alcohol-related disorder, which in addition is associated with 3% of all deaths in the world. In Brazil, harmful use and dependence on alcohol reach about 10% of the population, with alcohol being one of the main factors of disease and mortality. Although the medications currently used have some efficacy, the adverse effects and relatively long time of treatment are factors that may reduce patients' motivation to continue taking the medication correctly. Therefore, it is necessary to conduct research with new drugs for the treatment of alcoholism. Ibogaine is an alkaloid present in the bush Tabernanthe iboga (iboga), a plant from Central Africa traditionally used in countries such as Gabon and Cameroon. Animal studies and case series suggest that one or a few doses of ibogaine significantly reduce withdrawal symptoms and the intensity of use of various drugs, including opioids, psychostimulants, and alcohol. However, there are no controlled clinical studies that have explored these effects. The aim of the present study is to evaluate the safety, tolerability and efficacy of increasing doses of ibogaine in 12 alcoholic patients. Each patient will be hospitalized for 20 days and receive 3 increasing doses of ibogaine. The first 3 patients will receive oral doses of 20 to 400 mg of ibogaine in an open-label design. If the 3 higher doses (240, 320 and 400 mg) are well tolerated, the next 9 volunteers will receive these doses or placebo randomly. The volunteers will also be evaluated 7, 14 and 21 days and 1, 3, 6 and 12 months after leaving the hospital to monitor the consumption of alcohol and other drugs.

Official Title
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Tolerability and Efficacy of Ibogaine in the Treatment of Alcoholism: the First Randomized, Double-blind, Placebo-controlled, Escalating-dose, Phase 2 Trial

Conditions
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Alcoholism

Intervention / Treatment
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* Drug: Ibogaine Hydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Literate people Diagnosis of alcoholism assessed by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (SCID-V) History of at least two previous failed treatments for alcoholism (with drug use and / or psychotherapy) Signing the Free and Informed Consent Form. Exclusion Criteria: Presence of any psychiatric diagnosis (excluding alcohol / tobacco / nicotine abuse / dependence) assessed by the SCID-V Presence of clinical disease (especially cardiovascular and hepatic diseases), based on interview, physical and laboratory examination (hemogram and electrocardiogram, ECG) Absence of family or personal history of bipolar disorder and psychotic disorders Absence of recent symptoms of hypomania, mania or psychosis Non-literate people Pregnant or lactating women Recent use of illicit drugs (confirmed by examination in urine).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Ibogaine Hydrochloride 240 mg on day 1, placebo on day 4, placebo on day 7 | Drug: Ibogaine Hydrochloride<br>* The first 3 patients will receive oral doses of 20 to 400 mg of ibogaine in an open-label design. If the 3 higher doses (240, 320 and 400 mg) are well tolerated, the next 9 volunteers will receive these doses or placebo randomly in 3 different groups.<br>* Other names: Placebo;|
| Experimental: Group 2<br>Ibogaine Hydrochloride 240 mg on day 1, Ibogaine Hydrochloride 320 mg on day 4, placebo on day 7 | Drug: Ibogaine Hydrochloride<br>* The first 3 patients will receive oral doses of 20 to 400 mg of ibogaine in an open-label design. If the 3 higher doses (240, 320 and 400 mg) are well tolerated, the next 9 volunteers will receive these doses or placebo randomly in 3 different groups.<br>* Other names: Placebo;|
| Experimental: Group 3<br>Ibogaine Hydrochloride 240 mg on day 1, Ibogaine Hydrochloride 320 mg on day 4, Ibogaine Hydrochloride 400 mg on day 7 | Drug: Ibogaine Hydrochloride<br>* The first 3 patients will receive oral doses of 20 to 400 mg of ibogaine in an open-label design. If the 3 higher doses (240, 320 and 400 mg) are well tolerated, the next 9 volunteers will receive these doses or placebo randomly in 3 different groups.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time without using alcohol | Daily alcohol use | 0-1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective effects | Acute and subacute subjective effects | 0-12 hours | 
| Cardiovascular effects | Electrocardiogram | 0-72 hours |