Clinical trial NCT01189097: Combined Therapy of Methadone and Dextromethrophan
Official title: Combined Therapy of Methadone and Dextromethrophan: A Novel Strategy for the Treatment of Opioid Dependence
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Opioid Abuse
Lead sponsor: National Cheng-Kung University Hospital
Sponsor class: OTHER
First posted: 2010-08-26
Enrollment: 1500
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the pharmacological effects and outcomes of DM therapy with this add-on study.

And to determine the immunological changes between the baseline and the end point of the study.

Detailed description: Opioid dependence is a severe public health problem. Current efforts to taper individuals off opioid medications are limited due to a high relapse rate and lack of efficacy in relieving subjective symptoms. Methadone substitution therapies might decrease the criminal rate and increase the quality of life for individuals with opioid dependence, but the high drop-out rate and continuing use of methadone are major problems in the maintenance of therapy for opioid dependence. Studies in the pathogenesis of opioid dependence and additional behaviors need more focused attention.

Dextromethorphan (DM) is a noncompetitive N-methyl-D-aspartate receptor antagonist that has proven safety record for anti-tussive purpose. Previous studies demonstrated that DM may be useful in decreasing craving in animals (Huang, et al., 2003; Lue et al., 2007) and withdrawal tendencies in human with opioid dependence. In recent studies, DM has been reported to afford neuroprotection against endotoxin-induced dopaminergic neurotoxicity (Li et al. 2005; Liu et al. 2003; Zhang et al. 2004, 2005) which might be related to treatment for additictive behaviors. The purposes of this study are to examine whether DM is able to 1) reduce opioid tolerance and decrease methadone use; 2) reduce withdrawal symptoms; 3) decrease the relapse rate of opioid use, and 4) be an effective treatment for opioid dependence (and addictive behaviors).

This is a double-blinded, placebo-controlled, randomized, and parallel groups clinical research trial study. Subjects with opioid dependence are recruited from two different sources. One group will come from the list of current opioid users and will be required to stay on methadone treatment (opioid using group), and the second group will come from subjects who are forced to discontinue opioid use for more than one week (opioid free group).

In the opioid using group, add-on of DM or placebo treatment will proceed in a double-blind fashion for 12 weeks after completed structured diagnostic interview and adjusted methadone dose. In the opioid free group, subjects will take one-week placebo for the wash-out period first and then will be admitted into a double-blind DM/placebo only for 12 weeks. Both opioid using and opioid free groups will be examined weekly through urine tests for opioid use and will be assessed on a craving scale after the completion of the structured diagnostic interviews. We will measure the treatment response and side effects to clarify the curative effects of DM with the use of the double-blinded DM/placebo therapy design in both the opioid using and opioid free groups. Several psychological examinations, psychosocial questionnaires, tests for immune parameters, electrophysiological studies and genetic markers will be performed in this study. The interim analysis and decording of partial subjects who completed DM/placebo add-on treatment for three months will be performed in the end of first year.

Eligibility criteria: Inclusion Criteria:

1. Signed informed consent by patient or legal representative.
2. Male or female patient aged ≧18 and ≦65 years.
3. A diagnosis of opioid dependence according to DSM-IV criteria made by a specialist in psychiatry.
4. Patient or a reliable caregiver can be expected to ensure acceptable compliance and visit attendance for the duration of the study.

Exclusion Criteria:

1. Women of childbearing potential, not using adequate contraception as per investigator judgment or not willing to comply with contraception for the duration of the study.
2. Females who are pregnant or nursing.
3. Patient has received DM or other anti-inflammatory medications within 1 week prior to the first dose of the double-blinded medication.
4. Other major Axis-I DSM-IV diagnosis other than opioid dependence such as multiple substance dependence within 1 year prior to the fist dose of the double-blinded medication.
5. Current evidence of an uncontrolled and/or clinically significant medical condition, e.g., cardiac, hepatic and renal failure that would compromise patient safety or preclude study participation.
6. History of intolerance to methadone or DM.
7. History of sensitivity reaction (e.g., urticaria, angioedema, bronchospasm, severe rhinitis, anaphylactic shock) to DM.
8. Patient has received electroconvulsive therapy (ECT) within 4 weeks prior to the first dose of the double-blinded medication.
9. Increase in total SGOT, SGPT, gamma-GT, BUN and creatinine by more than 3X ULN (upper limit of normal).

Primary outcomes:
measure: Urinary examination
timeFrame: baseline
measure: Urinary examination
timeFrame: week 1
measure: Urinary examination
timeFrame: week2
measure: Urinary examination
timeFrame: week4
measure: Urinary examination
timeFrame: week8
measure: Urinary examination
timeFrame: week12
Secondary outcomes:
measure: cytokines
timeFrame: baseline
measure: cytokines
timeFrame: week1
measure: cytokines
timeFrame: week2
measure: cytokines
timeFrame: week4
measure: cytokines
timeFrame: week8
measure: cytokines
timeFrame: week12
Other outcomes:
Locations:
city: Tainan
country: Taiwan
facility: Ru-Band Lu
Study officials:
affiliation: National Cheng-Kung University Hospital
name: Ru-Band Lu, MD
role: PRINCIPAL_INVESTIGATOR
References: