A phase II trial of nerve growth factor for sensory neuropathy associated with HIV infection

J. C. McArthur, Constantin Yiannoutsos, D. M. Simpson, B. T. Adornato, E. J. Singer, H. Hollander, C. Marra, M. Rubin, B. A. Cohen, T. Tucker, B. A. Navia, G. Schifitto, D. Katzenstein, C. Rask, L. Zaborski, M. E. Smith, S. Shriver, L. Millar, D. B. Clifford

Research output: Contribution to journalArticle

223 Citations (Scopus)

Abstract

Objective: To evaluate the safety and efficacy of recombinant human nerve growth factor (rhNGF) in HIV-associated sensory neuropathy (SN) within a multicenter, placebo-controlled, randomized trial (ACTG 291). Background: SN affects 30% of individuals with AIDS, is worsened by neurotoxic antiretrovirals, and its treatment is often ineffective. NGF is trophic for small sensory neurons and stimulates the regeneration of damaged nerve fibers. Methods: A total of 270 patients with HIV-associated SN were randomized to receive placebo, 0.1 μg/kg rhNGF, or 0.3 μg/kg rhNGF by double-blinded subcutaneous injection twice weekly for 18 weeks. The primary outcome was change in self-reported neuropathic pain intensity (Gracely Pain Scale). Secondary outcomes included an assessment of global improvement in neuropathy by patients and investigators, neurologic examination, use of prescription analgesics, and quantitative sensory testing. In a subset, epidermal nerve fiber densities were determined in punch skin biopsies. Results: Both doses of NGF produced significant improvements in average and maximum daily pain compared with placebo. Positive treatment effects were also observed for global pain assessments (p = 0.001) and for pin sensitivity (p = 0.019). No treatment differences were found with respect to mood, analgesic use, or epidermal nerve fiber densities. Injection site pain was the most frequent adverse event, and resulted in unblinding in 39% of subjects. Severe transient myalgic pain occurred in eight patients, usually from accidental overdosing. There were no changes in HIV RNA levels or other laboratory indices. Conclusions: We found a positive effect of recombinant human nerve growth factor on neuropathic pain and pin sensitivity in HIV- associated sensory neuropathy, rhNGF was safe and well tolerated, but injection site pain was frequent.

Original languageEnglish (US)
Pages (from-to)1080-1088
Number of pages9
JournalNeurology
Volume54
Issue number5
StatePublished - Mar 14 2000
Externally publishedYes

Fingerprint

Nerve Growth Factor
HIV Infections
Pain
Nerve Fibers
HIV
Placebos
Neuralgia
Analgesics
Injections
Neurologic Examination
Sensory Receptor Cells
Pain Measurement
Subcutaneous Injections
Prescriptions
Regeneration
Acquired Immunodeficiency Syndrome
Therapeutics
Randomized Controlled Trials
Research Personnel
Outcome Assessment (Health Care)

Keywords

  • Analgesic
  • Dideoxynucleoside
  • HIV-associated sensory neuropathy
  • Nerve growth factor
  • Pain

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

McArthur, J. C., Yiannoutsos, C., Simpson, D. M., Adornato, B. T., Singer, E. J., Hollander, H., ... Clifford, D. B. (2000). A phase II trial of nerve growth factor for sensory neuropathy associated with HIV infection. Neurology, 54(5), 1080-1088.

A phase II trial of nerve growth factor for sensory neuropathy associated with HIV infection. / McArthur, J. C.; Yiannoutsos, Constantin; Simpson, D. M.; Adornato, B. T.; Singer, E. J.; Hollander, H.; Marra, C.; Rubin, M.; Cohen, B. A.; Tucker, T.; Navia, B. A.; Schifitto, G.; Katzenstein, D.; Rask, C.; Zaborski, L.; Smith, M. E.; Shriver, S.; Millar, L.; Clifford, D. B.

In: Neurology, Vol. 54, No. 5, 14.03.2000, p. 1080-1088.

Research output: Contribution to journalArticle

McArthur, JC, Yiannoutsos, C, Simpson, DM, Adornato, BT, Singer, EJ, Hollander, H, Marra, C, Rubin, M, Cohen, BA, Tucker, T, Navia, BA, Schifitto, G, Katzenstein, D, Rask, C, Zaborski, L, Smith, ME, Shriver, S, Millar, L & Clifford, DB 2000, 'A phase II trial of nerve growth factor for sensory neuropathy associated with HIV infection', Neurology, vol. 54, no. 5, pp. 1080-1088.
McArthur JC, Yiannoutsos C, Simpson DM, Adornato BT, Singer EJ, Hollander H et al. A phase II trial of nerve growth factor for sensory neuropathy associated with HIV infection. Neurology. 2000 Mar 14;54(5):1080-1088.
McArthur, J. C. ; Yiannoutsos, Constantin ; Simpson, D. M. ; Adornato, B. T. ; Singer, E. J. ; Hollander, H. ; Marra, C. ; Rubin, M. ; Cohen, B. A. ; Tucker, T. ; Navia, B. A. ; Schifitto, G. ; Katzenstein, D. ; Rask, C. ; Zaborski, L. ; Smith, M. E. ; Shriver, S. ; Millar, L. ; Clifford, D. B. / A phase II trial of nerve growth factor for sensory neuropathy associated with HIV infection. In: Neurology. 2000 ; Vol. 54, No. 5. pp. 1080-1088.
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AU - Singer, E. J.

AU - Hollander, H.

AU - Marra, C.

AU - Rubin, M.

AU - Cohen, B. A.

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N2 - Objective: To evaluate the safety and efficacy of recombinant human nerve growth factor (rhNGF) in HIV-associated sensory neuropathy (SN) within a multicenter, placebo-controlled, randomized trial (ACTG 291). Background: SN affects 30% of individuals with AIDS, is worsened by neurotoxic antiretrovirals, and its treatment is often ineffective. NGF is trophic for small sensory neurons and stimulates the regeneration of damaged nerve fibers. Methods: A total of 270 patients with HIV-associated SN were randomized to receive placebo, 0.1 μg/kg rhNGF, or 0.3 μg/kg rhNGF by double-blinded subcutaneous injection twice weekly for 18 weeks. The primary outcome was change in self-reported neuropathic pain intensity (Gracely Pain Scale). Secondary outcomes included an assessment of global improvement in neuropathy by patients and investigators, neurologic examination, use of prescription analgesics, and quantitative sensory testing. In a subset, epidermal nerve fiber densities were determined in punch skin biopsies. Results: Both doses of NGF produced significant improvements in average and maximum daily pain compared with placebo. Positive treatment effects were also observed for global pain assessments (p = 0.001) and for pin sensitivity (p = 0.019). No treatment differences were found with respect to mood, analgesic use, or epidermal nerve fiber densities. Injection site pain was the most frequent adverse event, and resulted in unblinding in 39% of subjects. Severe transient myalgic pain occurred in eight patients, usually from accidental overdosing. There were no changes in HIV RNA levels or other laboratory indices. Conclusions: We found a positive effect of recombinant human nerve growth factor on neuropathic pain and pin sensitivity in HIV- associated sensory neuropathy, rhNGF was safe and well tolerated, but injection site pain was frequent.

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