Clinical trial of melatonin for the treatment of neuropathic pain
| ISRCTN | ISRCTN16215617 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN16215617 |
- Submission date
- 26/04/2022
- Registration date
- 04/05/2022
- Last edited
- 29/09/2022
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Nervous System Diseases
Plain English Summary
Background and study aims
Sleep is commonly disturbed in patients with neuropathic pain; treatments that improve sleep may have an overall beneficial effect in patients with chronic pain. Given the need to identify effective, and safer, non-opioid pain treatments for chronic pain, the aim of this trial is to evaluate the effectiveness and safety of melatonin for the treatment of chronic neuropathic pain.
Who can participate?
Adults with chronic peripheral neuropathic pain
What does the study involve?
In this 10-week study, participants will receive two different sets of study treatments, each one consisting of a 4-week treatment period and a 1-week washout period (i.e. period when no pain medication is taken). During each treatment period participants will take one set of capsules. The number of capsules taken will be increased gradually over the first 3 weeks of each 5-week period. As the number of capsules increases some degree of pain relief may be experienced, as well as side effects such as drowsiness, and possibly other side effects. The goal will be to achieve the highest possible dose, yet a dose which does not cause intolerable side effects. Once that dose is reached, participants will continue to receive that dose for the entire fourth week of that treatment period. On the fifth week of each treatment period, the study medication will be stopped and participants will then continue to the next treatment period which will progress in a similar fashion.
In each of these treatment periods, the capsules will contain either filler (placebo) or melatonin. The two different treatment periods will come in random order. For example, participants may receive melatonin during the first treatment period and placebo during the second period, or, vice versa. Participants will not be told the contents of any of the contents during the study unless there is a medical emergency.
What are the possible benefits and risks of participating?
Given the known effects of melatonin in other pain conditions, there is some possibility that participants might enjoy meaningful sleep improvement and/or pain relief during parts of the study. It is also possible that participants gain no benefit from participating in the study. However, new knowledge gained from this study may improve the quality of pain management for other patients.
Growing evidence suggests that oral administration of melatonin is generally safe. A review including 37 melatonin studies reported side effects of daytime sleepiness (1.7%), headache (0.7%), other sleep-related side effects (0.7%), dizziness (0.7%) and hypothermia (0.6%) with very few reported serious adverse effects. However, if at any point during the study participants begin to feel any side effects that may be associated with taking this study treatment, they are urged to contact the study nurse and/or study physician immediately so that the dose can be adjusted appropriately.
Where is the study run from?
Queen’s University and Providence Care Hospital, Kingston, Ontario (Canada)
When is the study starting and how long is it expected to run for?
December 2020 to October 2025
Who is funding the study?
Physicians’ Services Incorporated Foundation (Canada)
Who is the main contact?
Dr Ian Gilron
gilroni@queensu.ca
Contact information
Principal Investigator
Dept Anesthesiology, Victory 2, KGH
76 Stuart Street
Kingston
K7L2V7
Canada
 ORCID ID |
0000-0002-5293-8792 |
|---|---|
| Phone | +1 (0)613 548 7827 |
| gilroni@queensu.ca |
Study information
| Study design | Double-blind placebo-controlled two-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 contact details to request a participant information sheet. |
| Scientific title | Melatonin for neuropathic pain |
| Study acronym | MNP |
| Study hypothesis | Oral administration of melatonin improves neuropathic pain and pain-related sleep disturbance. |
| Ethics approval(s) | Approval pending, Queen's University Research Ethics Board (Health Sciences and Affiliated Teaching Hospitals Research Ethics Board, 74 University Avenue, 251 Richardson Hall, Kingston, ON K7L 3N6, Canada, +1 (0)613-533-6000 ext. 78223; jennifer.couture@queensu.ca), ref: 6036266 |
| Condition | Chronic peripheral neuropathic pain |
| Intervention | Oral melatonin (3 mg capsules, or matching placebo) titrated over 21 days towards the maximal tolerated dose to a maximal dosage ceiling of 12 mg/day. Study participants will be randomized, in a double-blind fashion, to one of two possible treatment sequences (e.g. sequence 1: melatonin>placebo; sequence 2: placebo>melatonin;) such that each participant progresses through each of two 5-week treatment periods. Treatment periods will conclude with a 7-day complete washout. During each period, participants will receive study medication capsules - “melatonin” capsules which may contain melatonin 3 mg or an inert placebo. During the melatonin period, study medication will contain melatonin (3 mg capsules) and during the placebo, study medication will contain inert placebo. Melatonin, and melatonin placebo, study drug administration will occur only in the evenings. |
| Intervention type | Supplement |
| Primary outcome measure | Mean daily pain measured using a 0-10 numerical rating scale with 0 = “no pain”, 10 = “worst pain imaginable”, averaged over the “MTD fixed-dose week” (days 22-28) of each period |
| Secondary outcome measures | 1. Maximal tolerated doses of melatonin measured using research nurse report based on participant self-report at 1st and 3rd weeks of treatment, 4th week of treatment, washout 3 months post-trial completion 2. Frequency/severity of AEs measured using research nurse report based on participant self-report at screening, baseline, 1st and 3rd weeks of treatment, 4th week of treatment, washout 3 months post-trial completion 3. Global improvement, measured using the Patient Global Impression of Change (PGIC, a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention) at 1st and 3rd weeks of treatment, 4th week of treatment, washout 3 months post-trial completion 4. Pain dimensions, measured using the Short-form McGill Pain Questionnaire, an instrument to efficiently capture both the sensory and affective dimensions of pain, at pre-trial baseline and 4th week of treatment 5. Neuropathic pain symptoms, measured using the Neuropathic Pain Symptom Inventory, a 12-item self-questionnaire specifically designed to evaluate the different symptoms of neuropathic pain, at baseline and 4th week of treatment 6. Pain interference, measured using the Brief Pain Inventory, a survey instrument that measures how much pain has interfered with seven daily activities, including general activity, walking, work, mood, enjoyment of life, relations with others, and sleep, at baseline and 4th week of treatment 7. Mood, measured using the Beck Depression Inventory-II at screening, baseline and 4th week of treatment 8. Anxiety, measured using the Beck Anxiety Inventory at pre-trial baseline and 4th week of treatment 9. Quality of life, measured using the SF-36 survey at baseline and 4th week of treatment 10. Quality of blinding, measured using the Blinding questionnaires at 4th week of treatment 11. Acetaminophen consumption measured using participant self-report at 1st and 3rd weeks of treatment, 4th week of treatment, washout 3 months post-trial completion |
| Overall study start date | 13/12/2020 |
| Overall study end date | 31/10/2025 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 30 |
| Participant inclusion criteria | 1. Score of 4 or higher on the DN4 interview, a validated questionnaire that distinguishes between neuropathic and non-neuropathic pain.14 As indicated, investigations will be done to confirm NP diagnosis including, but not limited to, nerve conduction studies and electromyography. 2. Daily pain (≥4/10) for at least 3 months 3. AST/ALT ≤120% upper limit of normal 4. Creatinine clearance ≥60 ml/min 5. Glycosylated hemoglobin ≤9.5% 6. Necessary abilities, visual acuity, and language skills for questionnaire completion and phone communication with nurses |
| Participant exclusion criteria | 1. Major organ system disease 2. Cardiovascular autonomic neuropathy 3. Trigeminal neuralgia, complex regional pain syndrome or central neuropathic pain 4. Moderate to severe sedation or ataxia due to other required concomitant drugs 5. Allergy/hypersensitivity to study medications or any components in the study drug formulations or their containers 6. Seizure disorder 7. Other painful condition >50% as severe as their NP 8. A major, poorly controlled, psychiatric disorder, depression or suicidal ideation, or active substance use disorder 9. History of angioedema 10. Candidates who live alone and cannot assure daily contact with a friend, family member, or caregiver 11. Women of childbearing potential who will not receive a highly effective form of contraception (total abstinence, hormonal birth control methods, intrauterine devices, confirmed successful vasectomy of partner, double-barrier methods such as condom/diaphragm, etc.) and/or a positive pregnancy test at baseline (If a study participant becomes pregnant, she must stop using study medications immediately and will be withdrawn from the study) 12. Women who are breastfeeding or who plan to breastfeed 13. Regular daily administration of opioids at a dose greater than 90 mg morphine equivalents 14. Lack of a primary care physician |
| Recruitment start date | 01/09/2022 |
| Recruitment end date | 31/08/2025 |
Locations
Countries of recruitment
- Canada
Study participating centre
76 Stuart Street
Kingston
K7L2V7
Canada
Sponsor information
Charity
4773 Yonge Street, Suite 5G
North York
M2N 0G2
Canada
| Phone | +1 (0)416 226 6323 |
|---|---|
| psif@psifoundation.org | |
| Website | http://www.psifoundation.org/ |
"ROR" |
https://ror.org/0385yzn06 |
Funders
Funder type
Charity
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- PSI Foundation, PSI
- Location
- Canada
Results and Publications
| Intention to publish date | 01/01/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | Planned publication in a peer-reviewed journal |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made available as the research unit does not yet have the policies and procedures in place for public sharing of individual participant data. The data will be held in Kingston General Hospital (Canada). |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | 28/09/2022 | 29/09/2022 | Yes | No |
Editorial Notes
29/09/2022: Publication reference added.
29/04/2022: Trial's existence confirmed by the Physicians' Services Incorporated Foundation.
