Clinical Neuropharmacology of Pain in Spinal Cord Injury- Dextromethorphan Dose Response Clinical Trial

Study Overview
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Brief Summary
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This randomized, placebo-controlled, double-blind 4x4 crossover clinical trial was part of a larger NIH-funded study to evaluate the analgesic efficacy of three doses of chronic oral (PO) dextromethorphan compared to placebo in central neuropathic pain following spinal cord injury. Subjects' maximally tolerated doses (MTD) were first determined to establish individual dose-analgesic response relationships in a run-in period; following a washout period, subjects were then randomized to receive an order of four doses of dextromethorphan (including placebo) in a 4x4 Latin square cross-over design.

Official Title
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Clinical Neuropharmacology of Pain in Spinal Cord Injury- Dextromethorphan Dose Response Clinical Trial

Conditions
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Central Neuropathic Pain, Allodynia, Spinal Cord Injury

Intervention / Treatment
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* Drug: Dextromethorphan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female adults, age 18 to 70 with central neuropathic pain for a minimum of 3 months following SCI as confirmed by neurologic evaluation, with an average pain intensity score of at least moderate over at least 50% of the day for the 7 days prior to the screening visit and over the 7 days prior to starting study medication. Subjects used no medication or a stabilized medication regimen for chronic and well-controlled medical conditions Serum laboratory examination obtained at study entry: Liver function tests (albumin within 20% of normal, SGOT/SGPT within 50% of normal). For women of childbearing age: negative serum beta HCG. Postmenopausal women, or be physically incapable of childbearing, or be practicing an acceptable method of birth control. Normal cognitive function. Normal communicative ability (English). Ability to demonstrate competence in recording five times daily in pain diary for 1 week (with 100% compliance), and in completing required questionnaires. Signed informed consent. Exclusion Criteria: Pregnancy or breast-feeding. Renal or hepatic dysfunction. Significant cardiac disease (e.g. MI within 1 year). Signs or symptoms of central neurological disorder, excluding SCI. Severe psychological disorder requiring treatment. Concurrent use of monoamine oxidase inhibitors within 2 weeks prior to study entry. Use of known CYP2D6 (but not CYP3A4) inhibitors or inducers. History of hypersensitivity or intolerance to dextromethorphan or lidocaine. Chronic substance abuse, including alcohol. Participation in a study of an investigational drug or device within 30 days prior to screening for this study. Poor metabolizer of P450 2D6 substrates.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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 |
| --- | --- |
| Placebo Comparator: 0% MTD Dex<br>0% MTD Dextromethorphan | Drug: Dextromethorphan<br>* 0, 25, 50 and 100% of maximum tolerated dose, each administered over a 4 week period<br>|
| Experimental: 25% MTD Dex<br>25% MTD Dextromethorphan | Drug: Dextromethorphan<br>* 0, 25, 50 and 100% of maximum tolerated dose, each administered over a 4 week period<br>|
| Experimental: 50% MTD Dex<br>50% MTD Dextromethorphan | Drug: Dextromethorphan<br>* 0, 25, 50 and 100% of maximum tolerated dose, each administered over a 4 week period<br>|
| Experimental: 100% MTD Dex<br>100% MTD Dextromethorphan | Drug: Dextromethorphan<br>* 0, 25, 50 and 100% of maximum tolerated dose, each administered over a 4 week period<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Pain Intensity (Percent Change From Baseline) | Primary outcome was percent change from baseline in mean pain intensity (transformed Gracely Scale; 0-35). Baseline was defined as the week prior to randomization. The greater the percent change, the bigger the reduction in pain intensity. | 1st week of maintenance period (week prior to hospital admission for nested study; subjects traveled to Boston on days 6-7 of the maintenance period) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Satisfaction | Satisfaction with study treatment assessed over the 7 days prior to admission (5-point categorical scale) | Last week prior to admission (end of 1-week maintenance period) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic pain, central neuropathic pain, spinal cord injury, dextromethorphan, lidocaine, combination therapy, analgesia