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

Mass General Brigham

Status and phase: Completed; Phase 2

Conditions: Central Neuropathic Pain; Allodynia; Spinal Cord Injury

Treatments: Drug: Dextromethorphan

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01435798

2000p001387-A

R01NS041503

Details and patient eligibility

About

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.

Enrollment: 26 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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26 participants in 4 patient groups, including a placebo group

0% MTD Dex

Placebo Comparator group

Description:

0% MTD Dextromethorphan

Treatment:

Drug: Dextromethorphan

25% MTD Dex

Experimental group

Description:

25% MTD Dextromethorphan

Treatment:

Drug: Dextromethorphan

50% MTD Dex

Experimental group

Description:

50% MTD Dextromethorphan

Treatment:

Drug: Dextromethorphan

100% MTD Dex

Experimental group

Description:

100% MTD Dextromethorphan

Treatment:

Drug: Dextromethorphan