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

NCT02137213 | Completed Phase 2

• 1 other identifier: 083/2013
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Constipation

Keywords

Opioid-induced constipation; Methadone; Naloxone

Outcome Measures

Primary Outcomes (1)

• Severity of constipation symptoms

  Severity of constipation symptoms will be measured after one week of receiving methadone with naloxone and after one week of receiving methadone alone in both arms of the study.

  One week

Secondary Outcomes (1)

• Severity of opioid withdrawal symptoms

  Two weeks

Study Arms (2)

Arm A: Naloxone then placebo

EXPERIMENTAL

Subjects assigned to Arm A will receive methadone with naloxone for one week and then methadone with placebo for one week

Drug: Naloxone; Drug: Placebo

Arm B: Placebo then naloxone

EXPERIMENTAL

Subjects assigned to Arm B will receive methadone with placebo for one week and then methadone with naloxone for one week

Drug: Naloxone; Drug: Placebo

Interventions

Naloxone DRUG

Naloxone will be added to oral methadone preparation in methadone:naloxone ratio of 50:1

Also known as: Naloxone hydrochloride solution for injections 0.4 mg/ml

Arm A: Naloxone then placebo; Arm B: Placebo then naloxone

Placebo DRUG

Normal saline will be added to oral methadone preparations as placebo.

Also known as: Bacteriostatic normal saline

Arm A: Naloxone then placebo; Arm B: Placebo then naloxone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Centre for Addiction and Mental Health: lead
• Academic Health Science Centres: collaborator

Study Sites (1)

Centre for Addiction and Mental Health

Toronto, Ontario, M5V3R5, Canada

Location

Related Links

• Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teaching hospital, fully affiliated with the University of Toronto, and a PAHO/WHO Collaborating Centre.

MeSH Terms

Conditions

Constipation; Opioid-Induced Constipation

Interventions

Naloxone; Injections

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Andriy V Samokhvalov, MD, PhD

  Centre for Addiction and Mental Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 12, 2014
• First Posted: May 13, 2014
• Study Start: August 1, 2014
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: June 24, 2015

Record last verified: 2015-06

Locations

CA (1)