Condition category
Nervous System Diseases
Date applied
29/07/2009
Date assigned
03/08/2009
Last edited
05/05/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Ian Gilron

ORCID ID

Contact details

Department of Anesthesiology
Victory 2 Pavillion
Kingston General Hospital
76 Stuart Street
Kingston
K7L 2V7
Canada
+1 (0)613 548 7827
gilroni@queensu.ca

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

MCT-94187; ANAE-151-09

Study information

Scientific title

A double-blind, randomised controlled trial of nortriptyline, morphine, and their combination for neuropathic pain

Acronym

Study hypothesis

A combination of morphine and nortriptyline has superior analgesic efficacy versus either drug alone for reducing neuropathic pain.

Ethics approval

Queen's University Research Ethics Board, 23/03/2009

Study design

Double-blind randomised three-period crossover trial

Primary study design

Interventional

Secondary study design

Randomised cross over trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Neuropathic pain

Intervention

1. Morphine-nortryptyline combination
2. Morphine
3. Nortriptyline

As per a double-dummy, balanced Latin Square design, trial medications are administered orally in three different treatment periods. In each of the three periods, doses of nortriptyline, morphine and the two in combination are gradually titrated - over 24 days - towards each individual maximal tolerated dose and continued at that dose for seven days followed by an 11 day taper-washout period. Ceiling doses are 100 mg daily for both nortriptyline and morphine. Total duration of follow-up is 8 months.

Intervention type

Drug

Phase

Phase IV

Drug names

Morphine, nortriptyline

Primary outcome measures

Daily pain intensity. Patient follow-up for primary and secondary outcomes were recorded during treatment at maximal tolerated dose (i.e. day 25 - 31) for each treatment period.

Secondary outcome measures

1. Global pain relief, measures of sedation, constipation, other side effects and maximal tolerated drug doses
2. Short form McGill Pain Questionnaire-2
3. Brief Pain Inventory
4. Beck Depression Inventory
5. 36-item short form health survey (SF-36)
6. Blinding questionnaires
7. Acetaminophen consumption
8. Serum drug levels

Daily pain intensity. Patient follow-up for primary and secondary outcomes were recorded during treatment at maximal tolerated dose (i.e. day 25 - 31) for each treatment period.

Overall trial start date

01/11/2009

Overall trial end date

30/10/2012

Reason abandoned

Eligibility

Participant inclusion criteria

1. Neuropathic pain
2. Daily moderate (greater than or equal to 4/10) pain for at least 3 months
3. Adults aged 18 to 89 years, either sex
4. Liver function tests: alanine aminotransferase (ALT), aspartate aminotransferase (AST) less than 1.2 times upper limit of normal
5. Creatinine less than 1.5 times upper limit of normal
6. Negative serum beta-human chorionic gonadotrophin (B-HCG) for women of childbearing potential
7. Adequate birth control for all women of child-bearing potential
8. Sufficient cognitive function, visual acuity and English language skills to complete questionnaires and communicate verbally with the nursing staff to permit titration of the study drugs

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

71

Participant exclusion criteria

1. Painful condition as severe as, but distinct from presenting neuropathic pain
2. Pregnancy or lactation
3. End-stage kidney or liver disease
4. Moderate to severe heart disease (myocardial infarction [MI] within preceding year, unstable angina, cardiac conduction defect or congestive heart failure)
5. Cardiovascular autonomic neuropathy
6. Postural hypotension greater than 20 mmHg on initial assessment
7. Males with urinary symptoms attributable to benign prostatic hypertrophy
8. Patients who live alone and cannot assure daily contact with a friend, family member or caregiver
9. Angle-closure glaucoma
10. Ongoing administration of monoamine oxidase inhibitors, serotonin-specific reuptake inhibitors, serotonin-norepinephrine inhibitors
11. Any serious psychiatric disorder as diagnosed by a psychiatrist (including bipolar disorder)
12. Seizure disorder
13. Ongoing administration of anticonvulsants which induce cytochrome P450 enzymes (e.g. carbamazepine, oxcarbazepine, barbiturates and phenytoin) as well as rifampin
14. Hypersensitivity to, or previous intolerability of, any of the study medications
15. History of significant abuse of illicit drugs, prescription drugs or alcohol

Recruitment start date

01/11/2009

Recruitment end date

30/10/2012

Locations

Countries of recruitment

Canada

Trial participating centre

Kingston General Hospital
Kingston
K7L 2V7
Canada

Sponsor information

Organisation

Queen's University (Canada)

Sponsor details

Department of Anesthesiology
99 University Avenue
Kingston
Ontario
K7L 3N6
Canada

Sponsor type

University/education

Website

http://www.queensu.ca/

Funders

Funder type

Research organisation

Funder name

Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca (ref: MCT-94187)

Alternative name(s)

Instituts de Recherche en Santé du Canada, CIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

Canada

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/25749306

Publication citations

Additional files

Editorial Notes

05/05/2016: Publication reference added.