Clinical Neuropharmacology of Pain in Spinal Cord Injury

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Christine N. Sang, MD, MPH, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT01435798
First received: September 15, 2011
Last updated: September 16, 2011
Last verified: September 2011
  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:


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:

  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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
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:
Spinal Cord Injuries
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Trauma, Nervous System
Wounds and Injuries
Lidocaine
Dextromethorphan
Dexamethasone
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Anti-Arrhythmia Agents
Cardiovascular Agents
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Antitussive Agents
Respiratory System Agents
Excitatory Amino Acid Antagonists

ClinicalTrials.gov processed this record on October 01, 2014