Clinical Neuropharmacology of Pain in Spinal Cord Injury- Dextromethorphan/Lidocaine Combination 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 multiple dose-combinations of chronic oral (PO) dextromethorphan and intravenous (IV) lidocaine in central neuropathic pain following spinal cord injury.

Detailed Description
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This trial has several objectives: Primary Objective To determine which combination (dose-ratio) of dextromethorphan and lidocaine provides the best balance of pain reduction and toxicity. Secondary Objectives include To evaluate the analgesic efficacy of both dextromethorphan and lidocaine in attenuating pain related to central nervous system sensitization, specifically spontaneous pain, mechanical allodynia, and hyperalgesia.

Official Title
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Clinical Neuropharmacology of Pain in Spinal Cord Injury- Dextromethorphan/Lidocaine Combination (Factorial Design) Clinical Trial

Conditions
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Central Neuropathic Pain, Allodynia, Spinal Cord Injury

Intervention / Treatment
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* Drug: Dextromethorphan
* Drug: Lidocaine
* Drug: Placebo (Dextromethorphan)
* Drug: Placebo (Lidocaine)


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: Normal cognitive function. 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. History of hypersensitivity or intolerance to dextromethorphan or lidocaine. Participation in a study of an investigational drug or device within 30 days prior to screening for this study.

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: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo- 0mg/kg Lido<br>Placebo in combination with 0mg/kg LBM lidocaine | Drug: Placebo (Dextromethorphan)<br>* 0mg Dextromethorphan<br>Drug: Placebo (Lidocaine)<br>* 0mg/kg LBM Lidocaine<br>|
| Experimental: Placebo - 1mg/kg Lido<br>Placebo in combination with 1mg/kg LBM lidocaine | Drug: Lidocaine<br>* 0mg, 1mg, 2mg, and 4mg Lidocaine per kg of lean body mass (LBM), during each of the 4 dextromethorphan periods (placebo, low dose, medium dose, and high dose)<br>Drug: Placebo (Dextromethorphan)<br>* 0mg Dextromethorphan<br>|
| Experimental: Placebo - 2mg/kg Lido<br>Placebo in combination with 2mg/kg LBM lidocaine | Drug: Lidocaine<br>* 0mg, 1mg, 2mg, and 4mg Lidocaine per kg of lean body mass (LBM), during each of the 4 dextromethorphan periods (placebo, low dose, medium dose, and high dose)<br>Drug: Placebo (Dextromethorphan)<br>* 0mg Dextromethorphan<br>|
| Experimental: Placebo - 4mg/kg Lido<br>Placebo in combination with 4mg/kg LBM lidocaine | Drug: Lidocaine<br>* 0mg, 1mg, 2mg, and 4mg Lidocaine per kg of lean body mass (LBM), during each of the 4 dextromethorphan periods (placebo, low dose, medium dose, and high dose)<br>Drug: Placebo (Dextromethorphan)<br>* 0mg Dextromethorphan<br>|
| Experimental: Low Dose Dex - 0mg/kg Lido<br>Low dose dextromethorphan in combination with 0mg/kg LBM lidocaine | Drug: Dextromethorphan<br>* Administered in 4 periods (placebo, low dose, medium dose, and high dose) for each subject, relative to each subject's MTD)<br>Drug: Placebo (Lidocaine)<br>* 0mg/kg LBM Lidocaine<br>|
| Experimental: Low Dose Dex - 1mg/kg Lido<br>Low dose dextromethorphan in combination with 1mg/kg LBM lidocaine | Drug: Dextromethorphan<br>* Administered in 4 periods (placebo, low dose, medium dose, and high dose) for each subject, relative to each subject's MTD)<br>Drug: Lidocaine<br>* 0mg, 1mg, 2mg, and 4mg Lidocaine per kg of lean body mass (LBM), during each of the 4 dextromethorphan periods (placebo, low dose, medium dose, and high dose)<br>|
| Experimental: Low Dose Dex - 2mg/kg Lido<br>Low dose dextromethorphan in combination with 2mg/kg LBM lidocaine | Drug: Dextromethorphan<br>* Administered in 4 periods (placebo, low dose, medium dose, and high dose) for each subject, relative to each subject's MTD)<br>Drug: Lidocaine<br>* 0mg, 1mg, 2mg, and 4mg Lidocaine per kg of lean body mass (LBM), during each of the 4 dextromethorphan periods (placebo, low dose, medium dose, and high dose)<br>|
| Experimental: Low Dose Dex - 4mg/kg Lido<br>Low dose dextromethorphan in combination with 4mg/kg LBM lidocaine | Drug: Dextromethorphan<br>* Administered in 4 periods (placebo, low dose, medium dose, and high dose) for each subject, relative to each subject's MTD)<br>Drug: Lidocaine<br>* 0mg, 1mg, 2mg, and 4mg Lidocaine per kg of lean body mass (LBM), during each of the 4 dextromethorphan periods (placebo, low dose, medium dose, and high dose)<br>|
| Experimental: Medium Dose Dex - 0mg/kg Lido<br>Medium dose dextromethorphan in combination with 0mg/kg LBM lidocaine | Drug: Dextromethorphan<br>* Administered in 4 periods (placebo, low dose, medium dose, and high dose) for each subject, relative to each subject's MTD)<br>Drug: Placebo (Lidocaine)<br>* 0mg/kg LBM Lidocaine<br>|
| Experimental: Medium Dose Dex - 1mg/kg Lido<br>Medium dose dextromethorphan in combination with 1mg/kg LBM lidocaine | Drug: Dextromethorphan<br>* Administered in 4 periods (placebo, low dose, medium dose, and high dose) for each subject, relative to each subject's MTD)<br>Drug: Lidocaine<br>* 0mg, 1mg, 2mg, and 4mg Lidocaine per kg of lean body mass (LBM), during each of the 4 dextromethorphan periods (placebo, low dose, medium dose, and high dose)<br>|
| Experimental: Medium Dose Dex - 2mg/kg Lido<br>Medium dose dextromethorphan in combination with 2mg/kg LBM lidocaine | Drug: Dextromethorphan<br>* Administered in 4 periods (placebo, low dose, medium dose, and high dose) for each subject, relative to each subject's MTD)<br>Drug: Lidocaine<br>* 0mg, 1mg, 2mg, and 4mg Lidocaine per kg of lean body mass (LBM), during each of the 4 dextromethorphan periods (placebo, low dose, medium dose, and high dose)<br>|
| Experimental: Medium Dose Dex - 4mg/kg Lido<br>Medium dose dextromethorphan in combination with 4mg/kg LBM lidocaine | Drug: Dextromethorphan<br>* Administered in 4 periods (placebo, low dose, medium dose, and high dose) for each subject, relative to each subject's MTD)<br>Drug: Lidocaine<br>* 0mg, 1mg, 2mg, and 4mg Lidocaine per kg of lean body mass (LBM), during each of the 4 dextromethorphan periods (placebo, low dose, medium dose, and high dose)<br>|
| Experimental: High Dose Dex - 0mg/kg Lido<br>High dose dextromethorphan in combination with 0mg/kg LBM lidocaine | Drug: Dextromethorphan<br>* Administered in 4 periods (placebo, low dose, medium dose, and high dose) for each subject, relative to each subject's MTD)<br>Drug: Placebo (Lidocaine)<br>* 0mg/kg LBM Lidocaine<br>|
| Experimental: High Dose Dex - 1mg/kg Lido<br>High dose dextromethorphan in combination with 1mg/kg LBM lidocaine | Drug: Dextromethorphan<br>* Administered in 4 periods (placebo, low dose, medium dose, and high dose) for each subject, relative to each subject's MTD)<br>Drug: Lidocaine<br>* 0mg, 1mg, 2mg, and 4mg Lidocaine per kg of lean body mass (LBM), during each of the 4 dextromethorphan periods (placebo, low dose, medium dose, and high dose)<br>|
| Experimental: High Dose Dex - 2mg/kg Lido<br>High dose dextromethorphan in combination with 2mg/kg LBM lidocaine | Drug: Dextromethorphan<br>* Administered in 4 periods (placebo, low dose, medium dose, and high dose) for each subject, relative to each subject's MTD)<br>Drug: Lidocaine<br>* 0mg, 1mg, 2mg, and 4mg Lidocaine per kg of lean body mass (LBM), during each of the 4 dextromethorphan periods (placebo, low dose, medium dose, and high dose)<br>|
| Experimental: High Dose Dex - 4mg/kg Lido<br>High dose dextromethorphan in combination with 4mg/kg LBM lidocaine | Drug: Dextromethorphan<br>* Administered in 4 periods (placebo, low dose, medium dose, and high dose) for each subject, relative to each subject's MTD)<br>Drug: Lidocaine<br>* 0mg, 1mg, 2mg, and 4mg Lidocaine per kg of lean body mass (LBM), during each of the 4 dextromethorphan periods (placebo, low dose, medium dose, and high dose)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Peak Pain Intensity | Primary outcome was percent change from baseline in mean pain intensity at Cmax (transformed Gracely Scale; 0-35). Higher values on the Gracely scale represent greater pain intensity; the greater the percent change from baseline in mean pain intensity, the bigger the reduction in pain intensity. | 30 minutes post-infusion (Cmax) | 

 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