Chronic peripheral neuropathic pain Nervous System Diseases
Conditions
Interventions
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 rando
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 w
Sponsors
Physicians' Services Incorporated Foundation
Eligibility
Sex/Gender
All
Inclusion criteria
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
Exclusion criteria
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at baseline (If a study participant becomes pregnant, she must stop using study medications immediately and will be withdrawn from the study) 12.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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 us | — |
Countries
Canada
Outcome results
None listed