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

NCT01435798 | Completed Phase 2 Results DMC

• 2 other identifiers: 2000p001387-AR01NS041503
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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 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.

Conditions

Central Neuropathic Pain; Allodynia; Spinal Cord Injury

Keywords

chronic pain; central neuropathic pain; spinal cord injury; dextromethorphan; lidocaine; combination therapy; analgesia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Satisfaction

  Last week prior to admission (end of 1-week maintenance period)

Study Arms (4)

0% MTD Dex

PLACEBO COMPARATOR

0% MTD Dextromethorphan

Drug: Dextromethorphan

25% MTD Dex

EXPERIMENTAL

25% MTD Dextromethorphan

Drug: Dextromethorphan

50% MTD Dex

EXPERIMENTAL

50% MTD Dextromethorphan

Drug: Dextromethorphan

100% MTD Dex

EXPERIMENTAL

100% MTD Dextromethorphan

Drug: Dextromethorphan

Interventions

Dextromethorphan DRUG

0, 25, 50 and 100% of maximum tolerated dose, each administered over a 4 week period

0% MTD Dex; 100% MTD Dex; 25% MTD Dex; 50% MTD Dex

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

Translational Pain Research, Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Links

• Translational Pain Research, Brigham and Women's Hospital

MeSH Terms

Conditions

Hyperalgesia; Spinal Cord Injuries; Chronic Pain; Agnosia

Interventions

Dextromethorphan

Condition Hierarchy (Ancestors)

Somatosensory Disorders; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Spinal Cord Diseases; Central Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Pain; Perceptual Disorders; Neurobehavioral Manifestations

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Christine N. Sang, MD, MPH
• Organization: Translational Pain Research, Brigham and Women's Hospital

paintrials@partners.org

617-525-7246

Study Officials

• Christine N. Sang, MD, MPH

  Translational Pain Research, Brigham and Women's Hospital (Disclosure: Patent)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Translational Pain Research

Study Record Dates

• First Submitted: September 15, 2011
• First Posted: September 19, 2011
• Study Start: April 1, 2003
• Primary Completion: January 1, 2008
• Study Completion: January 1, 2008
• Last Updated: December 8, 2025
• Results First Posted: April 4, 2017

Record last verified: 2025-11

Locations

US (1)