Clinical Neuropharmacology of Pain in Spinal Cord Injury - Full Text View

Purpose

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.

Condition	Intervention	Phase
Neuralgia Allodynia Spinal Cord Injury	Drug: Dextromethorphan placebo, Lidocaine placebo Drug: Dex1Lido2 Drug: Dex1Lido3 Drug: Dex1Lido4 Drug: Dex2Lido1 Drug: Dex2Lido2 Drug: Dex2Lido3 Drug: Dex2Lido4 Drug: Dex3Lido1 Drug: Dex3Lido2 Drug: Dex3Lido3 Drug: Dex3Lido4 Drug: Dex4Lido1 Drug: Dex4Lido2 Drug: Dex4Lido3 Drug: Dex4Lido4	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Factorial Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Clinical Neuropharmacology of Pain in Spinal Cord Injury

Resource links provided by NLM:

MedlinePlus related topics: Spinal Cord Injuries

Drug Information available for: Dexamethasone Lidocaine hydrochloride Dextromethorphan hydrobromide Dextromethorphan Lidocaine Dexamethasone acetate Dexamethasone sodium phosphate Dextrose

U.S. FDA Resources

Further study details as provided by Brigham and Women's Hospital:

Primary Outcome Measures:

Mean pain intensity using pain intensity score [ Time Frame: Averaged over week 3 and week 4 of each treatment period ] [ Designated as safety issue: No ]
Mean pain intensity using the Gracely (log linear) Scale

Secondary Outcome Measures:

Global pain intensity over treatment period [ Time Frame: Averaged over week 3 and week 4 of each treatment period ] [ Designated as safety issue: No ]
Gracely Scale
Relief of spontaneous pain [ Time Frame: Serial measurements over 4h duration of treatment (infusion) ] [ Designated as safety issue: No ]
6-point categorical scale
Pain Intensity of 12 Pain Quality Descriptors [ Time Frame: Serial measurements over 4h duration of treatment (infusion) ] [ Designated as safety issue: No ]
Gracely Scale
Global Pain Relief [ Time Frame: Averaged over week 3 and week 4 of each treatment period ] [ Designated as safety issue: No ]
6-point categorical scale
Time to 50% and 100% pain relief [ Time Frame: Serial measurements over 4h duration of treatment (infusion) ] [ Designated as safety issue: No ]
Responses to quantitative sensory testing (thermal, electrical, tactile) [ Time Frame: Serial timepoints over 4h duration of treatment (infusion) ] [ Designated as safety issue: No ]
Change from baseline of various sensory stimuli (threshold/pain intensity) in areas of allodynia.
Number of Subjects with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Serial measurements over duration of each treatment ] [ Designated as safety issue: Yes ]
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
Spasticity Score [ Time Frame: Averaged over week 3 and week 4 of each treatment period ] [ Designated as safety issue: No ]
6-point categorical scale
Sleep Interference [ Time Frame: Averaged over week 3 and week 4 of each treatment period ] [ Designated as safety issue: No ]
6-point categorical scale
Quality of Life/Depression Inventories [ Time Frame: Averaged over week 3 and week 4 of each treatment period ] [ Designated as safety issue: No ]
Modified Duke Quality of Life Scale; Beck Depression Index
Subject Satisfaction Scores [ Time Frame: Serial measurements over 4h duration of treatment (infusion) ] [ Designated as safety issue: No ]
6-point categorical scale
Adequacy of blinding [ Time Frame: Assessed at the end of each treatment (4h) and at termination of study ] [ Designated as safety issue: No ]
Ability of each subject to correctly guess each treatment
Number of subjects reporting side effects [ Time Frame: Serial measurements over 4h duration of treatment (infusion) ] [ Designated as safety issue: Yes ]
For each self-reported side effect: intensity measured on 6-point categorical scale

Enrollment:	24
Study Start Date:	August 2000
Study Completion Date:	January 2008
Primary Completion Date:	January 2008 (Final data collection date for primary outcome measure)

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

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

Pregnancy or breast-feeding.
Renal or hepatic dysfunction.
Significant cardiac disease (MI within 1 year, unstable angina, or congestive heart failure).
Signs or symptoms of central neurological disorder, excluding SCI.
Severe psychological disorder requiring treatment, including depression.
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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01435798

Locations

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

Sponsors and Collaborators

Brigham and Women's Hospital

Investigators

Principal Investigator:

Christine N. Sang, MD, MPH

Translational Pain Research, Brigham and Women's Hospital

More Information

Additional Information:

Translational Pain Research, Brigham and Women's Hospital This link exits the ClinicalTrials.gov site

No publications provided

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:	RO1NS41503
Study First Received:	September 15, 2011
Last Updated:	September 16, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Brigham and Women's Hospital:

chronic pain
central neuropathic pain
spinal cord injury
dextromethorphan

lidocaine
combination therapy
analgesia

Additional relevant MeSH terms:

Neuralgia
Spinal Cord Injuries
Hyperalgesia
Pain
Neurologic Manifestations
Nervous System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Signs and Symptoms
Spinal Cord Diseases
Central Nervous System Diseases
Trauma, Nervous System
Wounds and Injuries
Somatosensory Disorders
Sensation Disorders

Dextromethorphan
Dexamethasone
Lidocaine
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Antitussive Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on June 18, 2013