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

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Central Neuropathic Pain; Allodynia; Spinal Cord Injury	Drug: Dextromethorphan	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	26 participants
Allocation:	Randomized
Intervention Model:	Crossover Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Clinical Neuropharmacology of Pain in Spinal Cord Injury- Dextromethorphan Dose Response Clinical Trial
Study Start Date :	April 2003
Actual Primary Completion Date :	January 2008
Actual Study Completion Date :	January 2008

Arms and Interventions

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Arm	Intervention/treatment
Placebo Comparator: 0% MTD Dex; 0% MTD Dextromethorphan	Drug: Dextromethorphan; 0, 25, 50 and 100% of maximum tolerated dose, each administered over a 4 week period
Experimental: 25% MTD Dex; 25% MTD Dextromethorphan	Drug: Dextromethorphan; 0, 25, 50 and 100% of maximum tolerated dose, each administered over a 4 week period
Experimental: 50% MTD Dex; 50% MTD Dextromethorphan	Drug: Dextromethorphan; 0, 25, 50 and 100% of maximum tolerated dose, each administered over a 4 week period
Experimental: 100% MTD Dex; 100% MTD Dextromethorphan	Drug: Dextromethorphan; 0, 25, 50 and 100% of maximum tolerated dose, each administered over a 4 week period

Outcome Measures

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Primary Outcome Measures :

1. Mean Pain Intensity (Percent Change From Baseline) [ Time Frame: 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) ]
   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.

Secondary Outcome Measures :

1. Satisfaction [ Time Frame: Last week prior to admission (end of 1-week maintenance period) ]
   Satisfaction with study treatment assessed over the 7 days prior to admission (5-point categorical scale)

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 70 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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:

   • Liver function tests (albumin within 20% of normal, SGOT/SGPT within 50% of normal).
   • For women of childbearing age: negative serum beta HCG.
4. Postmenopausal women, or be physically incapable of childbearing, or be practicing an acceptable method of birth control.
5. Normal cognitive function.
6. Normal communicative ability (English).
7. Ability to demonstrate competence in recording five times daily in pain diary for 1 week (with 100% compliance), and in completing required questionnaires.
8. 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. Concurrent use of monoamine oxidase inhibitors within 2 weeks prior to study entry.
7. Use of known CYP2D6 (but not CYP3A4) inhibitors or inducers.
8. History of hypersensitivity or intolerance to dextromethorphan or lidocaine.
9. Chronic substance abuse, including alcohol.
10. Participation in a study of an investigational drug or device within 30 days prior to screening for this study.
11. Poor metabolizer of P450 2D6 substrates.

Contacts and Locations

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Locations

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

Sponsors and Collaborators

Brigham and Women's Hospital

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)

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Translational Pain Research, Brigham and Women's Hospital 

Responsible Party:	Christine N. Sang, MD, MPH, Director, Translational Pain Research, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:	NCT01435798 History of Changes
Other Study ID Numbers:	R01NS041503 ( U.S. NIH Grant/Contract )
First Posted:	September 19, 2011
Results First Posted:	April 4, 2017
Last Update Posted:	April 4, 2017
Last Verified:	February 2017

Keywords provided by Christine N. Sang, MD, MPH, Brigham and Women's Hospital:

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

Additional relevant MeSH terms:

Wounds and Injuries; Spinal Cord Injuries; Neuralgia; Hyperalgesia; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Pain; Neurologic Manifestations; Peripheral Nervous System Diseases; Neuromuscular Diseases	Signs and Symptoms; Somatosensory Disorders; Sensation Disorders; Dextromethorphan; Antitussive Agents; Respiratory System Agents; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs