Comparing Opium Tincture (OT) With Methadone for Substitution Treatment of Opioid Dependence
Information source: University of British Columbia
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Opioid Dependence
Intervention: opium (Drug); methadone (Drug)
Phase: Phase 3
Status: Not yet recruiting
Sponsored by: University of British Columbia Official(s) and/or principal investigator(s): Michael R Kausz, MD, PhD, FRCPC, Principal Investigator, Affiliation: University of British Columbia Shahin Akhondzadeh, PhD.FBPharmacols., D. Sc., Principal Investigator, Affiliation: Tehran University of Medical Sciences
Overall contact: Mohammadali Nikoo, MD, Phone: 1 604-827-3975, Email: mnikoo@cheos.ubc.ca
Summary
Opioid-dependent patients seeking maintenance treatment will be recruited. Each participant
will be allocated to one of the two study groups with the equal chance of receiving either
opium tincture or methadone. Participants, clinical and research staff will not be aware of
the medication that each patient receives. This study aims to test whether opium tincture is
equally effective as methadone at retaining participants with opioid dependence in
substitution treatment.
Clinical Details
Official title: Comparison of Opium Tincture (OT) and Methadone for Maintenance Treatment of Opioid Dependence: A Randomized Double-blind Controlled Clinical Trial
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: retention in treatment
Secondary outcome: CravingWithdrawal symptoms physical health mental health cognitive function severity of substance use problem quality of life Client Satisfaction Abstinence adverse events Cost- effectiveness
Detailed description:
Purpose:
To compare the efficacy and safety of opium tincture (OT) with methadone syrup for
maintenance treatment of individuals with opioid-dependence.
Justification:
Currently, methadone is the gold standard for maintenance treatment of opioid use disorder.
Opium tincture (OT) could be a potential new treatment alternative for opioid dependence
disorder, and a promising solution to address the following issues:
1. Alternative treatment option As no single treatment is effective for all individuals
with opioid dependence, sufficiently diverse treatment options should be available.
Currently, treatment options for opioid dependence is not always effective in
addressing the addiction, neither after treatments which are offered based on clients'
choice, nor even after the current gold standard substitution drug, methadone.
2. Avoidance of overdose with methadone:
The long-acting nature of methadone, its narrow therapeutic window, its high potency
and associated lack of standard conversion ratio from and to other drugs, could result
in fatal overdose. In contrast, OT has a shorter half-life and lower potency compared
to methadone, which can account for a lower incidence of fatal overdose, especially in
patients at higher risk of overdose with currently prescribed medications. Thus, OT
could be an added treatment option to current available treatments such as
Buprenorphine/ Naloxone for maintenance treatment of patients with higher risk of
overdose.
3. Prolonged QT syndrome of methadone:
Maintenance treatment with methadone can cause serious, potentially fatal adverse
effects on the cardiac electrical conduction system leading to a prolonged QT interval
and predisposing patients to arrhythmias. As such, cardiac conduction co-morbidity is a
(relative) contraindication for the use of methadone as a maintenance treatment. Thus,
OT could be an added treatment option to current available treatments such as
buprenorphine or levomethadone for maintenance treatment of patients with cardiac
conduction defects.
4. Opium dependence pattern of substance use To date, studies on maintenance treatment of
opioid dependence have mostly been carried out on populations in which heroin is the
predominant substance of use and there is comparatively fewer data on opium dependent
patients. Opium tincture could be the treatment of choice in geographic areas with
higher prevalence of opium dependence as the predominant pattern of substance use, such
as Iran and some other Asian countries.
5. Traditional medicine and cultural acceptance: Being a traditional herbal remedy for
pain, opium tincture appears to be a more culturally acceptable alternative to
methadone in some parts of Southeast Asia.
6. Cost effectiveness: Possible cost effectiveness of OT for treatment of opioid use
disorder can make it a potential treatment of choice if its efficacy and safety profile
could be demonstrated through this RCT.
Research methods:
recruitment strategy: Following methods will be used to recruit participants: 1) Brochures
and flyers will be distributed in community outreach, general and mental hospitals, NGO-run
communities, colleges and universities, drop-in centers and specialized clinics for
treatment of participants with HIV and hepatitis C 2) Posters (same content as a brochures
and flyers) of the study will be stuck in the billboard of bus/subway, local stores,
hospitals, NGO-run communities, colleges and universities, as well as any specialized
health-care center for psychiatry or addiction treatments 3) there are two main NGO-run
communities in Tehran for treating opiate dependent patients in Tehran. Investigators will
use the initial contact letter to recruit from new patients attending these communities for
receiving treatment.
Sample size: Sample size calculation is based on non-inferiority design. In this study,
investigators aim to evaluate if OT is no less effective in terms of retention (the primary
outcome) than the gold standard, methadone. Previous clinical trials with methadone's 3-
month retention rate as their primary outcome, demonstrated a rate of approximately 80%.
Setting the type Ι error of 0. 05 and power of 80% with clinically acceptable margin of 10%,
the calculated sample size equals 100 participants in each treatment group. Considering a
dropout rate of 20%, total sample size will be 240, 120 participants randomized to each
group of the study. Statistical analysis plan: Retention in treatment will be compared
between two groups using Fisher's exact test considering P value ≤ 0. 05 as significant.
Secondary outcomes will be compared between two groups using Fisher's exact test,
independent samples T-test and One-way ANOVA test where applicable. Prediction of outcome
variables will be based on generalized linear model and generalized estimating equations
(GEE) model.
Eligibility
Minimum age: N/A.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Opioid dependence as confirmed by DSM V diagnostic criteria
- Willingness and ability to adhere to study protocol and follow-up schedule as
determined through the pre-randomization period
- Provide written informed consent.
- Females of childbearing capacity must agree to use an acceptable method of birth
control approved by the study investigator throughout the study.
Exclusion Criteria:
- Active participant in another treatment program for opioid dependence within 14 days
before inclusion in the study
- Severe hepatic impairment (decompensated liver disease), a contraindication for
methadone and its potential to precipitate hepatic encephalopathy.
- Hypersensitivity to methadone syrup or other ingredients in the formulation
- Pregnancy
- Severe chronic respiratory disease
- Head injury and raised intracranial pressure: Respiratory depressant effects (with
CO2 retention and secondary elevation of CSF pressure) may be markedly exaggerated in
the presence of head injury, or a preexisting increase in intracranial pressure. May
produce effects that obscure the clinical course in participants with head injuries.
- Biliary tract disease: may cause constriction of sphincter of Oddi.
- Monoamine oxidase inhibitors use within 14 days of the study
Locations and Contacts
Mohammadali Nikoo, MD, Phone: 1 604-827-3975, Email: mnikoo@cheos.ubc.ca
Roozbeh substance use treatment clinic, Tehran, Iran, Islamic Republic of; Not yet recruiting Afshar Amiri, MD, Phone: +989124246437, Email: amiriafshar@yahoo.com Amir Hooshang Bagheri Valoojerdi, MD, Phone: +989122191051, Email: drahbagheri@gmail.com Amir Hooshang Bagheri Valoojerdi, MD, Principal Investigator
Additional Information
Starting date: September 2015
Last updated: July 16, 2015
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