title: A phase II trial of nerve growth factor for sensory neuropathy associated with HIV infection. AIDS Clinical Trials Group Team 291.
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 microg/kg rhNGF, or 0.3 microg/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.
authors.affiliation: Department of Neurology, Johns Hopkins University, Baltimore, MD, USA. jm@jhmi.edu
authors.forename: J C
authors.initials: JC
authors.lastname: McArthur
authors.forename: C
authors.initials: C
authors.lastname: Yiannoutsos
authors.forename: D M
authors.initials: DM
authors.lastname: Simpson
authors.forename: B T
authors.initials: BT
authors.lastname: Adornato
authors.forename: E J
authors.initials: EJ
authors.lastname: Singer
authors.forename: H
authors.initials: H
authors.lastname: Hollander
authors.forename: C
authors.initials: C
authors.lastname: Marra
authors.forename: M
authors.initials: M
authors.lastname: Rubin
authors.forename: B A
authors.initials: BA
authors.lastname: Cohen
authors.forename: T
authors.initials: T
authors.lastname: Tucker
authors.forename: B A
authors.initials: BA
authors.lastname: Navia
authors.forename: G
authors.initials: G
authors.lastname: Schifitto
authors.forename: D
authors.initials: D
authors.lastname: Katzenstein
authors.forename: C
authors.initials: C
authors.lastname: Rask
authors.forename: L
authors.initials: L
authors.lastname: Zaborski
authors.forename: M E
authors.initials: ME
authors.lastname: Smith
authors.forename: S
authors.initials: S
authors.lastname: Shriver
authors.forename: L
authors.initials: L
authors.lastname: Millar
authors.forename: D B
authors.initials: DB
authors.lastname: Clifford
authors.forename: I J
authors.initials: IJ
authors.lastname: Karalnik
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000009:adverse effects / Q000627:therapeutic use*; D010146:Pain / Q000503:physiopathology; D010147:Pain Measurement; D010523:Peripheral Nervous System Diseases / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D020932:Nerve Growth Factor