Combination pharmacotherapy for the management of pain (2008)
| ISRCTN | ISRCTN04803491 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN04803491 |
| Secondary identifying numbers | MCT-94187; ANAE-151-09 |
- Submission date
- 29/07/2009
- Registration date
- 03/08/2009
- Last edited
- 05/05/2016
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nervous System Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr Ian Gilron
Scientific
Scientific
Department of Anesthesiology
Victory 2 Pavillion
Kingston General Hospital
76 Stuart Street
Kingston
K7L 2V7
Canada
| Phone | +1 (0)613 548 7827 |
|---|---|
| gilroni@queensu.ca |
Study information
| Study design | Double-blind randomised three-period crossover trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised cross over trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | A double-blind, randomised controlled trial of nortriptyline, morphine, and their combination for neuropathic pain |
| Study objectives | A combination of morphine and nortriptyline has superior analgesic efficacy versus either drug alone for reducing neuropathic pain. |
| Ethics approval(s) | Queen's University Research Ethics Board, 23/03/2009 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | 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 study start date | 01/11/2009 |
| Completion date | 30/10/2012 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 71 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 01/11/2009 |
| Date of final enrolment | 30/10/2012 |
Locations
Countries of recruitment
- Canada
Study participating centre
Kingston General Hospital
Kingston
K7L 2V7
Canada
K7L 2V7
Canada
Sponsor information
Queen's University (Canada)
University/education
University/education
Department of Anesthesiology
99 University Avenue
Kingston, Ontario
K7L 3N6
Canada
| Website | http://www.queensu.ca/ |
|---|---|
"ROR" |
https://ror.org/02y72wh86 |
Funders
Funder type
Research organisation
Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca (ref: MCT-94187)
Government organisation / National government
Government organisation / National government
- Alternative name(s)
- Instituts de Recherche en Santé du Canada, Canadian Institutes of Health Research (CIHR), CIHR_IRSC, Canadian Institutes of Health Research | Ottawa ON, CIHR, IRSC
- Location
- Canada
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/08/2015 | Yes | No |
Editorial Notes
05/05/2016: Publication reference added.
