Clinical trial NCT01435798: Clinical Neuropharmacology of Pain in Spinal Cord Injury- Dextromethorphan Dose Response Clinical Trial
Official title: Clinical Neuropharmacology of Pain in Spinal Cord Injury- Dextromethorphan Dose Response Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Central Neuropathic Pain
Allodynia
Spinal Cord Injury
Keywords: chronic pain
central neuropathic pain
spinal cord injury
dextromethorphan
lidocaine
combination therapy
analgesia
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2011-09-19
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Mean Pain Intensity (Percent Change From Baseline)
timeFrame: 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:
measure: Satisfaction
timeFrame: Last week prior to admission (end of 1-week maintenance period)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Translational Pain Research, Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Translational Pain Research, Brigham and Women's Hospital (Disclosure: Patent)
name: Christine N. Sang, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: