Clinical Neuropharmacology of Pain in Spinal Cord Injury- Dextromethorphan/Lidocaine Combination Clinical Trial

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

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.

Study Overview

• Status: Completed
• Conditions: Spinal Cord Injury; Allodynia; Central Neuropathic Pain
• Intervention / Treatment: Drug: Placebo (Dextromethorphan); Drug: Placebo (Lidocaine); Drug: Lidocaine; Drug: Dextromethorphan

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Translational Pain Research, Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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.
2. Subjects used no medication or a stabilized medication regimen for chronic and well-controlled medical conditions
3. Serum laboratory examination obtained at study entry:
4. Normal cognitive function.
5. Signed informed consent.

Exclusion Criteria:

1. Pregnancy or breast-feeding.
2. Renal or hepatic dysfunction.
3. Significant cardiac disease (e.g. MI within 1 year).
4. Signs or symptoms of central neurological disorder, excluding SCI.
5. Severe psychological disorder requiring treatment.
6. History of hypersensitivity or intolerance to dextromethorphan or lidocaine.
7. Participation in a study of an investigational drug or device within 30 days prior to screening for this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

16

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo- 0mg/kg Lido; Placebo in combination with 0mg/kg LBM lidocaine	Drug: Placebo (Dextromethorphan); 0mg Dextromethorphan; Drug: Placebo (Lidocaine); 0mg/kg LBM Lidocaine
Experimental: Placebo - 1mg/kg Lido; Placebo in combination with 1mg/kg LBM lidocaine	Drug: Placebo (Dextromethorphan); 0mg Dextromethorphan; Drug: Lidocaine; 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)
Experimental: Placebo - 2mg/kg Lido; Placebo in combination with 2mg/kg LBM lidocaine	Drug: Placebo (Dextromethorphan); 0mg Dextromethorphan; Drug: Lidocaine; 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)
Experimental: Placebo - 4mg/kg Lido; Placebo in combination with 4mg/kg LBM lidocaine	Drug: Placebo (Dextromethorphan); 0mg Dextromethorphan; Drug: Lidocaine; 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)
Experimental: Low Dose Dex - 0mg/kg Lido; Low dose dextromethorphan in combination with 0mg/kg LBM lidocaine	Drug: Placebo (Lidocaine); 0mg/kg LBM Lidocaine; Drug: Dextromethorphan; Administered in 4 periods (placebo, low dose, medium dose, and high dose) for each subject, relative to each subject's MTD)
Experimental: Low Dose Dex - 1mg/kg Lido; Low dose dextromethorphan in combination with 1mg/kg LBM lidocaine	Drug: Lidocaine; 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); Drug: Dextromethorphan; Administered in 4 periods (placebo, low dose, medium dose, and high dose) for each subject, relative to each subject's MTD)
Experimental: Low Dose Dex - 2mg/kg Lido; Low dose dextromethorphan in combination with 2mg/kg LBM lidocaine	Drug: Lidocaine; 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); Drug: Dextromethorphan; Administered in 4 periods (placebo, low dose, medium dose, and high dose) for each subject, relative to each subject's MTD)
Experimental: Low Dose Dex - 4mg/kg Lido; Low dose dextromethorphan in combination with 4mg/kg LBM lidocaine	Drug: Lidocaine; 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); Drug: Dextromethorphan; Administered in 4 periods (placebo, low dose, medium dose, and high dose) for each subject, relative to each subject's MTD)
Experimental: Medium Dose Dex - 0mg/kg Lido; Medium dose dextromethorphan in combination with 0mg/kg LBM lidocaine	Drug: Placebo (Lidocaine); 0mg/kg LBM Lidocaine; Drug: Dextromethorphan; Administered in 4 periods (placebo, low dose, medium dose, and high dose) for each subject, relative to each subject's MTD)
Experimental: Medium Dose Dex - 1mg/kg Lido; Medium dose dextromethorphan in combination with 1mg/kg LBM lidocaine	Drug: Lidocaine; 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); Drug: Dextromethorphan; Administered in 4 periods (placebo, low dose, medium dose, and high dose) for each subject, relative to each subject's MTD)
Experimental: Medium Dose Dex - 2mg/kg Lido; Medium dose dextromethorphan in combination with 2mg/kg LBM lidocaine	Drug: Lidocaine; 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); Drug: Dextromethorphan; Administered in 4 periods (placebo, low dose, medium dose, and high dose) for each subject, relative to each subject's MTD)
Experimental: Medium Dose Dex - 4mg/kg Lido; Medium dose dextromethorphan in combination with 4mg/kg LBM lidocaine	Drug: Lidocaine; 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); Drug: Dextromethorphan; Administered in 4 periods (placebo, low dose, medium dose, and high dose) for each subject, relative to each subject's MTD)
Experimental: High Dose Dex - 0mg/kg Lido; High dose dextromethorphan in combination with 0mg/kg LBM lidocaine	Drug: Placebo (Lidocaine); 0mg/kg LBM Lidocaine; Drug: Dextromethorphan; Administered in 4 periods (placebo, low dose, medium dose, and high dose) for each subject, relative to each subject's MTD)
Experimental: High Dose Dex - 1mg/kg Lido; High dose dextromethorphan in combination with 1mg/kg LBM lidocaine	Drug: Lidocaine; 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); Drug: Dextromethorphan; Administered in 4 periods (placebo, low dose, medium dose, and high dose) for each subject, relative to each subject's MTD)
Experimental: High Dose Dex - 2mg/kg Lido; High dose dextromethorphan in combination with 2mg/kg LBM lidocaine	Drug: Lidocaine; 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); Drug: Dextromethorphan; Administered in 4 periods (placebo, low dose, medium dose, and high dose) for each subject, relative to each subject's MTD)
Experimental: High Dose Dex - 4mg/kg Lido; High dose dextromethorphan in combination with 4mg/kg LBM lidocaine	Drug: Lidocaine; 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); Drug: Dextromethorphan; Administered in 4 periods (placebo, low dose, medium dose, and high dose) for each subject, relative to each subject's MTD)

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Christine N. Sang, MD, MPH, Translational Pain Research, Brigham and Women's Hospital (Disclosure: Patent)

Publications and helpful links

Helpful Links

• Translational Pain Research, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start: April 1, 2003
• Primary Completion (Actual): January 1, 2008
• Study Completion (Actual): January 1, 2008

Study Registration Dates

• First Submitted: August 13, 2014
• First Submitted That Met QC Criteria: August 15, 2014
• First Posted (Estimated): August 18, 2014

Study Record Updates

• Last Update Posted (Actual): December 8, 2025
• Last Update Submitted That Met QC Criteria: November 20, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: chronic pain; lidocaine; combination therapy; analgesia; spinal cord injury; dextromethorphan; central neuropathic pain
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Neurobehavioral Manifestations; Sensation Disorders; Trauma, Nervous System; Spinal Cord Diseases; Somatosensory Disorders; Perceptual Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Chronic Pain; Spinal Cord Injuries; Hyperalgesia; Agnosia; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Alkaloids; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Anilides; Amides; Aniline Compounds; Amines; Acetanilides; Heterocyclic Compounds, 4 or More Rings; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Phenanthrenes; Lidocaine; Dextromethorphan
• Other Study ID Numbers: 2000p001387; R01NS041503 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No