Clinical Neuropharmacology of Pain in Spinal Cord Injury

Spinal Cord Injury Clinical Trial

Official title:

Clinical Neuropharmacology of Pain in Spinal Cord Injury

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01435798
• Other study ID #: RO1NS41503
• Status: Completed
• Phase: Phase 2
• First received: September 15, 2011
• Last updated: September 16, 2011
• Start date: August 2000
• Est. completion date: January 2008

Study information

• Verified date: September 2011
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study is an NIH-funded two-part clinical trial to determine the best dose-ratio of individual subjects with central neuropathic pain following spinal cord injury (SCI), when two compounds with different target mechanisms are administered as combination therapy. The investigators will first determine each subjects' maximally tolerated dose (MTD) of chronic oral (PO) administration of dextromethorphan (Dex); the investigators will then randomize subjects to receive multiple dose-combinations of dextromethorphan and lidocaine (Lido). The investigators will be able to determine each subject's individual dose-response relationship for the separate compounds with adequate power, and thus also confirm the analgesic efficacy of high dose dextromethorphan and lidocaine, each in central neuropathic pain.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: January 2008
• Est. primary completion date: January 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Healthy male or female adults, age 18 to 70 with persistent pain and touch-evoked allodynia 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 must use no medication or a stabilized medication regimen for chronic and well-controlled conditions such as hypertension, allergies, stable endocrinopathies (e.g. hypothyroidism), etc.

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 (IUD, hormones, or barrier method plus spermicide).

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 (MI within 1 year, unstable angina, or congestive heart failure).

4. Signs or symptoms of central neurological disorder, excluding SCI.

5. Severe psychological disorder requiring treatment, including depression.

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Allodynia
• Neuralgia
• Spinal Cord Injuries
• Spinal Cord Injury

Intervention

Drug:
• Dextromethorphan placebo, Lidocaine placebo
All PO drugs given QID; all IV drugs delivered over 30 minutes.
• Dex1Lido2
All PO drugs given QID; all IV drugs delivered over 30 minutes.
• Dex1Lido3
All PO drugs given QID; all IV drugs delivered over 30 minutes.
• Dex1Lido4
All PO drugs given QID; all IV drugs delivered over 30 minutes.
• Dex2Lido1
All PO drugs given QID; all IV drugs delivered over 30 minutes.
• Dex2Lido2
All PO drugs given QID; all IV drugs delivered over 30 minutes.
• Dex2Lido3
All PO drugs given QID; all IV drugs delivered over 30 minutes.
• Dex2Lido4
All PO drugs given QID; all IV drugs delivered over 30 minutes.
• Dex3Lido1
All PO drugs given QID; all IV drugs delivered over 30 minutes.
• Dex3Lido2
All PO drugs given QID; all IV drugs delivered over 30 minutes.
• Dex3Lido3
All PO drugs given QID; all IV drugs delivered over 30 minutes.
• Dex3Lido4
All PO drugs given QID; all IV drugs delivered over 30 minutes.
• Dex4Lido1
All PO drugs given QID; all IV drugs delivered over 30 minutes.
• Dex4Lido2
All PO drugs given QID; all IV drugs delivered over 30 minutes.
• Dex4Lido3
All PO drugs given QID; all IV drugs delivered over 30 minutes.
• Dex4Lido4
All PO drugs given QID; all IV drugs delivered over 30 minutes.

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Brigham and Women's Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean pain intensity using pain intensity score	Mean pain intensity using the Gracely (log linear) Scale	Averaged over week 3 and week 4 of each treatment period	No
Secondary	Global pain intensity over treatment period	Gracely Scale	Averaged over week 3 and week 4 of each treatment period	No
Secondary	Relief of spontaneous pain	6-point categorical scale	Serial measurements over 4h duration of treatment (infusion)	No
Secondary	Pain Intensity of 12 Pain Quality Descriptors	Gracely Scale	Serial measurements over 4h duration of treatment (infusion)	No
Secondary	Global Pain Relief	6-point categorical scale	Averaged over week 3 and week 4 of each treatment period	No
Secondary	Time to 50% and 100% pain relief		Serial measurements over 4h duration of treatment (infusion)	No
Secondary	Responses to quantitative sensory testing (thermal, electrical, tactile)	Change from baseline of various sensory stimuli (threshold/pain intensity) in areas of allodynia.	Serial timepoints over 4h duration of treatment (infusion)	No
Secondary	Number of Subjects with Adverse Events as a Measure of Safety and Tolerability	Change from baseline in various safety parameters: Monitoring (hemodynamic; heart rate, rhythm, blood pressure, oxygen saturation, respiratory rate, temperature) Physical exam (neurologic) Cognition (attention; short and long term memory); Change from baseline in: Hematology profile, coagulation profile, electrolytes, liver function tests, renal function tests Urinalysis	Serial measurements over duration of each treatment	Yes
Secondary	Spasticity Score	6-point categorical scale	Averaged over week 3 and week 4 of each treatment period	No
Secondary	Sleep Interference	6-point categorical scale	Averaged over week 3 and week 4 of each treatment period	No
Secondary	Quality of Life/Depression Inventories	Modified Duke Quality of Life Scale; Beck Depression Index	Averaged over week 3 and week 4 of each treatment period	No
Secondary	Subject Satisfaction Scores	6-point categorical scale	Serial measurements over 4h duration of treatment (infusion)	No
Secondary	Adequacy of blinding	Ability of each subject to correctly guess each treatment	Assessed at the end of each treatment (4h) and at termination of study	No
Secondary	Number of subjects reporting side effects	For each self-reported side effect: intensity measured on 6-point categorical scale	Serial measurements over 4h duration of treatment (infusion)	Yes

External Links

•   Translational Pain Research, Brigham and Women's Hospital