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Efficient assessment of neuropathic pain drugs in patients with small fiber sensory neuropathies.

Abstract

We sought to develop an enrichment crossover study design that would allow us to efficiently evaluate and compare promising candidate neuropathic pain drugs. We evaluated the efficacy of gabapentin or tramadol vs. active placebo (diphenhydramine) in subjects with biopsy-proven painful idiopathic small fiber neuropathy (SFN) who were self-reported gabapentin responders. Eligible subjects entered two single blind run-in phases. In the first phase (Period A), subjects were treated with single blinded gabapentin at their prestudy dose followed by a second run-in phase (Period B) in which they were treated with diphenhydramine active placebo. Subjects with >or=3 pain and a >or=30% increase in pain intensity in Period B compared to Period A were then randomized to a double-blind three period cross over trial of gabapentin at pre study dosage, tramadol 50mg QID and diphenhydramine 50mgqhs. Of the 59 subjects enrolled, 41 subjects were excluded: Twenty-three had an insufficient rise in pain intensity in Period B; eight had skin biopsies that did not confirm SFN. Eighteen subjects were randomized into the double-blind, crossover phase. There was a significant treatment effect of gabapentin vs. diphenhydramine (p=0.001) and tramadol vs. diphenhydramine (p=0.018) by the before-bed daily pain score averaged over the final 7 days of each treatment period. We conclude that gabapentin and tramadol were effective in the treatment of painful SFN and that this experimental enrichment paradigm is attractive to screen potential neuropathic pain compounds for efficacy in proof-of-concept studies.

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  • Authors+Show Affiliations

    ,

    Merck & Co., Inc., UG4C-96 P.O. Box 100, North Wales, PA 19454, USA. tony_ho@merck.com

    , , , ,

    Source

    Pain 141:1-2 2009 Jan pg 19-24

    MeSH

    Adolescent
    Adult
    Amines
    Analgesics
    Cross-Over Studies
    Cyclohexanecarboxylic Acids
    Diphenhydramine
    Double-Blind Method
    Female
    Gabapentin
    Humans
    Male
    Middle Aged
    Neuralgia
    Pain Measurement
    Pain Threshold
    Peripheral Nervous System Diseases
    Single-Blind Method
    Sleep Wake Disorders
    Tramadol
    Young Adult
    gamma-Aminobutyric Acid

    Pub Type(s)

    Comparative Study
    Journal Article
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    19013718

    Citation

    Ho, T W., et al. "Efficient Assessment of Neuropathic Pain Drugs in Patients With Small Fiber Sensory Neuropathies." Pain, vol. 141, no. 1-2, 2009, pp. 19-24.
    Ho TW, Backonja M, Ma J, et al. Efficient assessment of neuropathic pain drugs in patients with small fiber sensory neuropathies. Pain. 2009;141(1-2):19-24.
    Ho, T. W., Backonja, M., Ma, J., Leibensperger, H., Froman, S., & Polydefkis, M. (2009). Efficient assessment of neuropathic pain drugs in patients with small fiber sensory neuropathies. Pain, 141(1-2), pp. 19-24. doi:10.1016/j.pain.2008.07.013.
    Ho TW, et al. Efficient Assessment of Neuropathic Pain Drugs in Patients With Small Fiber Sensory Neuropathies. Pain. 2009;141(1-2):19-24. PubMed PMID: 19013718.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Efficient assessment of neuropathic pain drugs in patients with small fiber sensory neuropathies. AU - Ho,T W, AU - Backonja,M, AU - Ma,J, AU - Leibensperger,H, AU - Froman,S, AU - Polydefkis,M, Y1 - 2008/11/14/ PY - 2008/01/11/received PY - 2008/07/02/revised PY - 2008/07/14/accepted PY - 2008/11/18/pubmed PY - 2009/4/9/medline PY - 2008/11/18/entrez SP - 19 EP - 24 JF - Pain JO - Pain VL - 141 IS - 1-2 N2 - We sought to develop an enrichment crossover study design that would allow us to efficiently evaluate and compare promising candidate neuropathic pain drugs. We evaluated the efficacy of gabapentin or tramadol vs. active placebo (diphenhydramine) in subjects with biopsy-proven painful idiopathic small fiber neuropathy (SFN) who were self-reported gabapentin responders. Eligible subjects entered two single blind run-in phases. In the first phase (Period A), subjects were treated with single blinded gabapentin at their prestudy dose followed by a second run-in phase (Period B) in which they were treated with diphenhydramine active placebo. Subjects with >or=3 pain and a >or=30% increase in pain intensity in Period B compared to Period A were then randomized to a double-blind three period cross over trial of gabapentin at pre study dosage, tramadol 50mg QID and diphenhydramine 50mgqhs. Of the 59 subjects enrolled, 41 subjects were excluded: Twenty-three had an insufficient rise in pain intensity in Period B; eight had skin biopsies that did not confirm SFN. Eighteen subjects were randomized into the double-blind, crossover phase. There was a significant treatment effect of gabapentin vs. diphenhydramine (p=0.001) and tramadol vs. diphenhydramine (p=0.018) by the before-bed daily pain score averaged over the final 7 days of each treatment period. We conclude that gabapentin and tramadol were effective in the treatment of painful SFN and that this experimental enrichment paradigm is attractive to screen potential neuropathic pain compounds for efficacy in proof-of-concept studies. SN - 1872-6623 UR - https://www.unboundmedicine.com/medline/citation/19013718/Efficient_assessment_of_neuropathic_pain_drugs_in_patients_with_small_fiber_sensory_neuropathies_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3959(08)00402-8 DB - PRIME DP - Unbound Medicine ER -