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

Sponsor
Brigham and Women's Hospital (Other)
Overall Status
Completed
CT.gov ID
NCT01435798
Collaborator
National Institute of Neurological Disorders and Stroke (NINDS) (NIH)
26
1
4
57
0.5

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
26 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Clinical Neuropharmacology of Pain in Spinal Cord Injury- Dextromethorphan Dose Response Clinical Trial
Study Start Date :
Apr 1, 2003
Actual Primary Completion Date :
Jan 1, 2008
Actual Study Completion Date :
Jan 1, 2008

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: 0% MTD Dex

0% MTD Dextromethorphan

Drug: Dextromethorphan
0, 25, 50 and 100% of maximum tolerated dose, each administered over a 4 week period

Experimental: 25% MTD Dex

25% MTD Dextromethorphan

Drug: Dextromethorphan
0, 25, 50 and 100% of maximum tolerated dose, each administered over a 4 week period

Experimental: 50% MTD Dex

50% MTD Dextromethorphan

Drug: Dextromethorphan
0, 25, 50 and 100% of maximum tolerated dose, each administered over a 4 week period

Experimental: 100% MTD Dex

100% MTD Dextromethorphan

Drug: Dextromethorphan
0, 25, 50 and 100% of maximum tolerated dose, each administered over a 4 week period

Outcome Measures

Primary Outcome Measures

  1. Mean Pain Intensity (Percent Change From Baseline) [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)]

    Primary outcome was percent change from baseline in mean pain intensity (transformed Gracely Scale; 0-35). Baseline was defined as the week prior to randomization. The greater the percent change, the bigger the reduction in pain intensity.

Secondary Outcome Measures

  1. Satisfaction [Last week prior to admission (end of 1-week maintenance period)]

    Satisfaction with study treatment assessed over the 7 days prior to admission (5-point categorical scale)

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

  1. Postmenopausal women, or be physically incapable of childbearing, or be practicing an acceptable method of birth control.

  2. Normal cognitive function.

  3. Normal communicative ability (English).

  4. Ability to demonstrate competence in recording five times daily in pain diary for 1 week (with 100% compliance), and in completing required questionnaires.

  5. 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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Translational Pain Research, Brigham and Women's Hospital Boston Massachusetts United States 02115

Sponsors and Collaborators

  • Brigham and Women's Hospital
  • National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

  • Principal Investigator: Christine N. Sang, MD, MPH, Translational Pain Research, Brigham and Women's Hospital (Disclosure: Patent)

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Christine N. Sang, MD, MPH, Director, Translational Pain Research, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT01435798
Other Study ID Numbers:
  • R01NS041503
First Posted:
Sep 19, 2011
Last Update Posted:
Apr 4, 2017
Last Verified:
Feb 1, 2017
Keywords provided by Christine N. Sang, MD, MPH, Director, Translational Pain Research, Brigham and Women's Hospital
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details Subjects were recruited nationally from referring physicians, through advertisements, and through existing databases.
Pre-assignment Detail During the screening visit, P450 2D6 phenotype status was determined for each subject to identify drug-metabolizing capacity; those who were P450 2D6 poor-metabolizers were excluded. Following screen, each subject entered a dose escalation period to determine his/her maximum tolerated dose (MTD), prior to randomization.
Arm/Group Title Dextromethorphan Dose Response (DDR) Clinical Trial
Arm/Group Description Each subject received four doses of dextromethorphan; 0% (placebo), 25%, 50%, and 100% of the maximum tolerated dose in a balanced randomized order. Each dose was administered for a period of 28 days; on day 21 of each phase, subjects traveled to the study site to undergo study procedures in a nested clinical trial (not described here).
Period Title: Overall Study
STARTED 26
0% MTD 25
25% MTD 26
50% MTD 25
100% MTD 25
COMPLETED 25
NOT COMPLETED 1

Baseline Characteristics

Arm/Group Title Dextromethorphan Dose Response Clinical Trial
Arm/Group Description Each subject received four doses of dextromethorphan; 0% (placebo), 25%, 50%, and 100% of the maximum tolerated dose in a balanced randomized order. Each dose was administered for a period of 28 days; on day 21 of each phase, subjects traveled to the study site to undergo study procedures in a nested clinical trial (not described here).
Overall Participants 26
Age (Count of Participants)
<=18 years
0
0%
Between 18 and 65 years
25
96.2%
>=65 years
1
3.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
46.84
(11.32)
Sex: Female, Male (Count of Participants)
Female
14
53.8%
Male
12
46.2%
Region of Enrollment (participants) [Number]
North America
26
100%

Outcome Measures

1. Primary Outcome
Title Mean Pain Intensity (Percent Change From Baseline)
Description Primary outcome was percent change from baseline in mean pain intensity (transformed Gracely Scale; 0-35). Baseline was defined as the week prior to randomization. The greater the percent change, the bigger the reduction in pain intensity.
Time Frame 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)

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title 0% MTD Dex 25% MTD Dex 50% MTD Dex 100% MTD Dex
Arm/Group Description 0% (placebo) of maximum tolerated dose of dextromethorphan; dose was administered for a period of 28 days, and on day 21, subjects traveled to the study site to undergo additional study procedures. 25% of maximum tolerated dose of dextromethorphan; dose was administered for a period of 28 days, and on day 21, subjects traveled to the study site to undergo additional study procedures. 50% of maximum tolerated dose of dextromethorphan; dose was administered for a period of 28 days, and on day 21, subjects traveled to the study site to undergo additional study procedures. 100% of maximum tolerated dose of dextromethorphan; dose was administered for a period of 28 days, and on day 21, subjects traveled to the study site to undergo additional study procedures.
Measure Participants 25 26 25 25
Mean (Standard Error) [Percent change from baseline]
-0.006
(0.01)
-0.018
(0.005)
-0.073
(0.01)
-0.24
(0.01)
2. Secondary Outcome
Title Satisfaction
Description Satisfaction with study treatment assessed over the 7 days prior to admission (5-point categorical scale)
Time Frame Last week prior to admission (end of 1-week maintenance period)

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title 0% MTD Dex 25% MTD Dex 50% MTD Dex 100% MTD Dex
Arm/Group Description 0% (placebo) of maximum tolerated dose of dextromethorphan; dose was administered for a period of 28 days, and on day 21, subjects traveled to the study site to undergo additional study procedures. 25% of maximum tolerated dose of dextromethorphan; dose was administered for a period of 28 days, and on day 21, subjects traveled to the study site to undergo additional study procedures. 50% of maximum tolerated dose of dextromethorphan; dose was administered for a period of 28 days, and on day 21, subjects traveled to the study site to undergo additional study procedures. 100% of maximum tolerated dose of dextromethorphan; dose was administered for a period of 28 days, and on day 21, subjects traveled to the study site to undergo additional study procedures.
Measure Participants 25 26 25 25
Not Satisfied
20
76.9%
18
NaN
16
NaN
9
NaN
Fairly Satisfied
2
7.7%
5
NaN
7
NaN
8
NaN
Satisfied
3
11.5%
2
NaN
0
NaN
5
NaN
Very/Extremely Satisfied
0
0%
1
NaN
2
NaN
3
NaN

Adverse Events

Time Frame Adverse event data were collected post-dose through the end of treatment in each arm.
Adverse Event Reporting Description All anticipated and unanticipated post-dose adverse events that were possibly, probably, or definitely related to the study drug are reported.
Arm/Group Title 0% MTD Dex 25% MTD Dex 50% MTD Dex 100% MTD Dex
Arm/Group Description 0% (placebo) of maximum tolerated dose of dextromethorphan; dose was administered for a period of 28 days, and on day 21, subjects traveled to the study site to undergo additional study procedures. 25% of maximum tolerated dose of dextromethorphan; dose was administered for a period of 28 days, and on day 21, subjects traveled to the study site to undergo additional study procedures. 50% of maximum tolerated dose of dextromethorphan; dose was administered for a period of 28 days, and on day 21, subjects traveled to the study site to undergo additional study procedures. 100% of maximum tolerated dose of dextromethorphan; dose was administered for a period of 28 days, and on day 21, subjects traveled to the study site to undergo additional study procedures.
All Cause Mortality
0% MTD Dex 25% MTD Dex 50% MTD Dex 100% MTD Dex
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN) / (NaN) / (NaN)
Serious Adverse Events
0% MTD Dex 25% MTD Dex 50% MTD Dex 100% MTD Dex
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/25 (0%) 0/26 (0%) 0/25 (0%) 0/25 (0%)
Other (Not Including Serious) Adverse Events
0% MTD Dex 25% MTD Dex 50% MTD Dex 100% MTD Dex
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 2/25 (8%) 3/26 (11.5%) 2/25 (8%) 16/25 (64%)
Ear and labyrinth disorders
Tinnitis 0/25 (0%) 0 0/26 (0%) 0 2/25 (8%) 2 0/25 (0%) 0
Nervous system disorders
Sedation 0/25 (0%) 0 0/26 (0%) 0 0/25 (0%) 0 8/25 (32%) 8
Blurry Vision 0/25 (0%) 0 0/26 (0%) 0 0/25 (0%) 0 3/25 (12%) 3
Interference with Alertness 2/25 (8%) 2 3/26 (11.5%) 3 0/25 (0%) 0 3/25 (12%) 3
Interference with Ability to Drive 0/25 (0%) 0 0/26 (0%) 0 0/25 (0%) 0 2/25 (8%) 2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title Christine N. Sang, MD, MPH
Organization Translational Pain Research, Brigham and Women's Hospital
Phone 617-525-7246
Email paintrials@partners.org
Responsible Party:
Christine N. Sang, MD, MPH, Director, Translational Pain Research, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT01435798
Other Study ID Numbers:
  • R01NS041503
First Posted:
Sep 19, 2011
Last Update Posted:
Apr 4, 2017
Last Verified:
Feb 1, 2017