Imipramine and Pregabalin Combination in Painful Polyneuropathy

Study Overview
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Brief Summary
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Polyneuropathy of different etiologies is often associated with pain and the standard treatment for this type of pain is gabapentinoids or antidepressants. The hypothesis of this study is that the combination of the gabapentinoid pregabalin and the antidepressant imipramine will provide better pain relief than the single compounds alone. This is a randomized, placebo-controlled, double-blind, 4-way, cross-over trial of pregabalin 300 mg/day, imipramine 75 mg/day and their combination versus placebo. The study will include 60 patients and the treatment outcome will be pain intensity as measured by numeric rating scales.

Official Title
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Randomised, Double-blind, Placebo-controlled Trial of the Effect of the Combination of Imipramine and Pregabalin for the Treatment of Painful Polyneuropathy

Conditions
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Polyneuropathy

Intervention / Treatment
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* Drug: Imipramine
* Drug: Pregabalin
* Drug: Imipramine, pregabalin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 20 - 85 years. Characteristic symptoms of polyneuropathy for at least 6 months. Polyneuropathy diagnosis confirmed by typical clinical signs (distal sensory disturbance/lack of distal deep tendon reflexes) and/or electrophysiological tests and/or abnormal quantitative sensory tests. Total pain intensity rating of at least 4 on a 0-10 points numeric rating scale. Pain present at least 4 days a week. For diabetics: diabetes diagnosis for at least 6 months and stable metabolic control for at least 3 months. For other secondary polyneuropathies: stable for at least 6 months. For fertile females: adequate anticonceptive treatment. Written informed consent. Exclusion Criteria: Other cause of pain. Contraindications against imipramine. Allergic reactions towards imipramine or pregabalin. Known adverse reactions during imipramine or pregabalin treatment. Pregnancy. Severe systemic disease. Ongoing treatment with antidepressants, antipsychotics, anticonvulsants, opioids, propranolol, kinidine, monoamine oxidase inhibitor. Inability to follow study protocol.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Imipramine<br>Imipramine tablets and placebo capsules to pregabalin | Drug: Imipramine<br>* Tablet 25 mg, 3 tablets evening (extensive metabolizers) or 1 tablet evening (poor metabolizers), daily, 5 weeks<br>* Other names: Imipramin DAK;|
| Active Comparator: Pregabalin<br>Pregabalin capsules and placebo tablets to imipramine | Drug: Pregabalin<br>* Capsule 75 mg, 2 capsules twice daily, daily, 5 weeks<br>* Other names: Lyrica;|
| Experimental: Imipramine plus pregabalin<br>Imipramine tablets and pregabalin capsules | Drug: Imipramine, pregabalin<br>* Imipramine: tablet 25 mg, 3 tablets evening (extensive metabolizers) or 1 tablet evening (poor metabolizers), daily, 5 weeks Pregabalin: capsule 75 mg, 2 capsules twice daily, daily, 5 weeks<br>* Other names: Lyrica;|
| Placebo Comparator: Placebo<br>Placebo tablets to imipramine and placebo capsules to pregabalin | Drug: Placebo<br>* Placebo tablets to imipramine 25 mg, 3 or 1 tablet evening, daily, 5 weeks Placebo capsules to pregabalin 75 mg, 2 capsules daily, daily, 5 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total pain intensity as measured by numeric rating scale 0-10 points. |  | Median of ratings from last week of each treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Verbal pain relief scale with 6 classes |  | End of each treatment period | 
| Specific pain symptom rated by numeric rating scales 0-10 points |  | Median of ratings from last week of each treatment period | 
| Rating of evoked pains symptoms (pressure, brush, repetitive pin-prick, cold) as measured by numeric rating scales 0-10 points |  | End of each treatment period | 
| Sleep disturbance as measured by numeric rating scale 0-10 points |  | Median of ratings from last week of each treatment period | 
| Consumption of escape medication (number of tablets of paracetamol) |  | Total consumption during last week of each treatment period | 
| Health related quality of life (SF-36) |  | End of each treatment period | 
| Major Depression Inventory (MDI) |  | End of each treament period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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polyneuropathy, neuropathic pain, treatment