Feasibility Study of Oral Naloxone for Treatment of Methadone-induced Constipation

• Status: Completed
• Trial end date: 2015-03-01
• Target enrollment: 0
• Participant gender: All

Summary

At least 30% of patients receiving methadone maintenance therapy (MMT) are suffering from constipation that often affects effectiveness of MMT and increases its impact on health care system. Existing treatments include several over-the-counter medications which do not target the pathobiological basis of opioid-induced constipation and have limited effectiveness. At the same time well-known medication, naloxone, was already shown to help with constipation in patients receiving methadone for chronic pain, but was never tried in patients receiving methadone for opioid dependence. This study is aimed to try naloxone for treatment of opioid-induced constipation in MMT settings.

The investigators will enroll 20 patients receiving MMT and suffering from opioid-induced constipation. The study has a crossover design - all patients will receive one week of their regular methadone doses and one week of their regular methadone doses with naloxone added. Normal saline will be added to methadone-only formulations as placebo. Order of the weeks will be chosen randomly. Both subjects and investigators will be blinded to the study condition (i.e. whether naloxone or normal saline is added to methadone preparation on a given week).

Primary hypothesis: Patients receiving combination of oral methadone/naloxone in ratio 50:1 will have less severe symptoms of constipation compared to those receiving methadone only.

Secondary hypothesis: Addition of oral naloxone to methadone in a ratio 50:1 will not cause clinically significant opioid withdrawal symptoms.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Centre for Addiction and Mental Health
• Collaborator: Academic Health Science Centres
• Treatments: Methadone; Naloxone

Criteria

Inclusion Criteria:

• 18 years of age or older

• must be a registered CAMH methadone maintenance program client

• must be in a maintenance stage of MMT program (at least 6 weeks in MMT)

• stable methadone dose taken once daily (no methadone dose change in the past 4 weeks)

• methadone dose between 20 mg and 140 mg/day (normal range of methadone doses prescribed in CAMH opioid dependence clinic)

• Bowel Functioning Index score ≥ 30 (reference range for non-constipated patients is 0-28.8)

• less than 3 bowel movements in the week prior to initiation

Exclusion Criteria:

• patients prescribed opioids other than methadone

• patients who use opioids recreationally

• patients prescribed methadone for pain management

• patients receiving methadone in split doses

• pregnancy

• allergy or sensitivity to naloxone

• current gastrointestinal disorder (chronic colitis, Crohn disease etc.)

• taking medications with known strong anticholinergic effects (e.g. amitryptiline)