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

Phase 2

Completed

• Conditions: Central Neuropathic Pain; Allodynia; Spinal Cord Injury
• Interventions: Drug: Placebo (Dextromethorphan); Drug: Lidocaine; Drug: Dextromethorphan; Drug: Placebo (Lidocaine)

• Registration Number: NCT02218203
• Lead Sponsor: Brigham and Women's Hospital

Brief Summary

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

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 Timeline

• Study Start: 2003-04
• Primary Completion: 2008-01
• Study Completion: 2008-01
• Study First Submitted: 2014-08-13
• Study First Submitted QC: 2014-08-15
• Study First Posted: 2014-08-18
• Results First Submitted: 2017-03-29
• Status Verified: 2018-03
• Results First Submitted QC: 2018-03-21
• Last Update Submitted: 2018-03-21
• Results First Posted: 2018-03-22
• Last Update Posted: 2018-03-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Placebo- 0mg/kg Lido	Placebo (Dextromethorphan)	Placebo in combination with 0mg/kg LBM lidocaine
Placebo- 0mg/kg Lido	Placebo (Lidocaine)	Placebo in combination with 0mg/kg LBM lidocaine
Placebo - 1mg/kg Lido	Lidocaine	Placebo in combination with 1mg/kg LBM lidocaine
Placebo - 1mg/kg Lido	Placebo (Dextromethorphan)	Placebo in combination with 1mg/kg LBM lidocaine
Placebo - 2mg/kg Lido	Placebo (Dextromethorphan)	Placebo in combination with 2mg/kg LBM lidocaine
Placebo - 4mg/kg Lido	Placebo (Dextromethorphan)	Placebo in combination with 4mg/kg LBM lidocaine
Low Dose Dex - 0mg/kg Lido	Dextromethorphan	Low dose dextromethorphan in combination with 0mg/kg LBM lidocaine
Low Dose Dex - 0mg/kg Lido	Placebo (Lidocaine)	Low dose dextromethorphan in combination with 0mg/kg LBM lidocaine
Low Dose Dex - 1mg/kg Lido	Dextromethorphan	Low dose dextromethorphan in combination with 1mg/kg LBM lidocaine
Low Dose Dex - 1mg/kg Lido	Lidocaine	Low dose dextromethorphan in combination with 1mg/kg LBM lidocaine
Low Dose Dex - 2mg/kg Lido	Dextromethorphan	Low dose dextromethorphan in combination with 2mg/kg LBM lidocaine
Low Dose Dex - 2mg/kg Lido	Lidocaine	Low dose dextromethorphan in combination with 2mg/kg LBM lidocaine
Low Dose Dex - 4mg/kg Lido	Dextromethorphan	Low dose dextromethorphan in combination with 4mg/kg LBM lidocaine
Low Dose Dex - 4mg/kg Lido	Lidocaine	Low dose dextromethorphan in combination with 4mg/kg LBM lidocaine
Medium Dose Dex - 0mg/kg Lido	Dextromethorphan	Medium dose dextromethorphan in combination with 0mg/kg LBM lidocaine
Medium Dose Dex - 0mg/kg Lido	Placebo (Lidocaine)	Medium dose dextromethorphan in combination with 0mg/kg LBM lidocaine
Medium Dose Dex - 1mg/kg Lido	Dextromethorphan	Medium dose dextromethorphan in combination with 1mg/kg LBM lidocaine
Medium Dose Dex - 2mg/kg Lido	Dextromethorphan	Medium dose dextromethorphan in combination with 2mg/kg LBM lidocaine
High Dose Dex - 0mg/kg Lido	Placebo (Lidocaine)	High dose dextromethorphan in combination with 0mg/kg LBM lidocaine
High Dose Dex - 2mg/kg Lido	Lidocaine	High dose dextromethorphan in combination with 2mg/kg LBM lidocaine
High Dose Dex - 4mg/kg Lido	Dextromethorphan	High dose dextromethorphan in combination with 4mg/kg LBM lidocaine
High Dose Dex - 4mg/kg Lido	Lidocaine	High dose dextromethorphan in combination with 4mg/kg LBM lidocaine
Placebo - 4mg/kg Lido	Lidocaine	Placebo in combination with 4mg/kg LBM lidocaine
Placebo - 2mg/kg Lido	Lidocaine	Placebo in combination with 2mg/kg LBM lidocaine
Medium Dose Dex - 1mg/kg Lido	Lidocaine	Medium dose dextromethorphan in combination with 1mg/kg LBM lidocaine
Medium Dose Dex - 2mg/kg Lido	Lidocaine	Medium dose dextromethorphan in combination with 2mg/kg LBM lidocaine
Medium Dose Dex - 4mg/kg Lido	Dextromethorphan	Medium dose dextromethorphan in combination with 4mg/kg LBM lidocaine
Medium Dose Dex - 4mg/kg Lido	Lidocaine	Medium dose dextromethorphan in combination with 4mg/kg LBM lidocaine
High Dose Dex - 0mg/kg Lido	Dextromethorphan	High dose dextromethorphan in combination with 0mg/kg LBM lidocaine
High Dose Dex - 1mg/kg Lido	Lidocaine	High dose dextromethorphan in combination with 1mg/kg LBM lidocaine
High Dose Dex - 1mg/kg Lido	Dextromethorphan	High dose dextromethorphan in combination with 1mg/kg LBM lidocaine
High Dose Dex - 2mg/kg Lido	Dextromethorphan	High dose dextromethorphan in combination with 2mg/kg LBM lidocaine

Primary Outcome Measures

Name	Time	Method
Percent Change in Peak Pain Intensity	30 minutes post-infusion (Cmax)	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.

Trial Locations

Locations (1)

Translational Pain Research, Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States