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 measure
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 (if study stopped)
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
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, IRSC
Funding Body Type
government organisation
Funding Body Subtype
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
Basic results (scientific)
Publication list
2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/25749306