A Phase II, Double-Blind Trial of Recombinant Human Nerve Growth Factor for Treatment of HIV-Associated Sensory Neuropathy

To assess the efficacy, safety, and tolerability of recombinant human nerve growth factor ( rhNGF ) in the treatment of HIV-associated sensory neuropathy. AS PER AMENDMENT 5/6/97: To compare the change in viral load between the double-blind phase baseline and week 4 in placebo and active rhNGF recipients. To ensure that rhNGF does not induce an increase in viral load compared with viral load changes seen with placebo.

Up to now, treatments for HIV-associated sensory neuropathy have been symptomatic, relying on pain-modifying agents or membrane-stabilizing drugs. Because nerve growth factor is important in the development and maintenance of sympathetic and sensory neurons and their outgrowths, it is proposed that recombinant human nerve growth factor may provide a specific restorative treatment for HIV-associated painful sensory neuropathy.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Peripheral Nervous System Disease
• Intervention / Treatment: Drug: Nerve Growth Factor, Recombinant Human

Detailed Description

Up to now, treatments for HIV-associated sensory neuropathy have been symptomatic, relying on pain-modifying agents or membrane-stabilizing drugs. Because nerve growth factor is important in the development and maintenance of sympathetic and sensory neurons and their outgrowths, it is proposed that recombinant human nerve growth factor may provide a specific restorative treatment for HIV-associated painful sensory neuropathy.

Patients are randomized to receive either rhNGF at one of two doses or placebo, administered subcutaneously twice weekly for 18 weeks. Patients are stratified into three groups within their regimens by use of didanosine, zalcitabine, or stavudine as follows: current use vs. discontinued between 8 and 26 weeks before randomization vs. never used or discontinued use at least 26 weeks before randomization. Patients will assess their pain daily using the Gracely Pain Scale. AS PER AMENDMENT 5/6/97: After completion of the double-blind phase (18 weeks on treatment followed by 4 weeks off treatment), patients may receive open-label, active drug treatment according to their previously assigned regimen for an additional 48 weeks.

• Study Type: Interventional
• Enrollment: 270
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA CARE Center CRS
    • San Mateo, California, United States
      • San Mateo County AIDS Program
    • Stanford, California, United States, 943055107
      • Stanford CRS
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University CRS
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Adult AIDS CRS
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess - East Campus A0102 CRS
  • Missouri
    • Saint Louis, Missouri, United States
      • Washington U CRS
  • New York
    • New York, New York, United States, 10016
      • NY Univ. HIV/AIDS CRS
    • New York, New York, United States
      • Cornell University A2201
    • Rochester, New York, United States, 14642
      • Univ. of Rochester ACTG CRS
  • North Carolina
    • Chapel Hill, North Carolina, United States, 275997215
      • Unc Aids Crs
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Case CRS
    • Columbus, Ohio, United States, 432101228
      • The Ohio State Univ. AIDS CRS
  • Washington
    • Seattle, Washington, United States, 981224304
      • University of Washington AIDS CRS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

Concurrent Medication:

Allowed:

• Maintenance treatment of CMV retinitis, MAI bacteremia, or cryptococcal meningitis is permitted.
• Local therapy for Kaposi's sarcoma.

Patients must have:

• Evidence of HIV antibodies documented by a licensed ELISA and a second, FDA-approved, confirmatory test.
• Diagnosis of HIV-associated, predominantly sensory neuropathy by a neurologist.
• Willingness and ability to complete the pain and medication log and competence to assess pain level throughout the study.

Prior Medication:

Allowed:

• History of stable-dose (defined as no more than 50% increase or decrease in dose) antiretroviral therapy for eight weeks before randomization, including the following:
• didanosine, zalcitabine, stavudine, lamivudine, protease inhibitors, and antiretrovirals available through expanded access trials.
• Chemotherapeutic drugs other than neurotoxic systemic chemotherapeutic agents within 30 days prior to randomization.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Presence of acute, active, opportunistic infection, except oral thrush; oral, genital or rectal herpes; and MAI bacteremia within two weeks before randomization.
• Evidence of another contributing cause for peripheral neuropathy, including:
• diabetes mellitus, hereditary neuropathy, current vitamin B12 deficiency and no supplementation or supplementation <= 3 months, or treatment with any drug that might contribute to sensory neuropathy.
• Major active psychiatric disorder (depression is allowed provided patient has received a stable antidepressant regimen for at least four weeks before randomization).
• Current active malignancy. NOTE: Malignancies in remission that do not require further treatment or Kaposi's sarcoma requiring only local treatment are allowed.
• Any conditions, including dementia and myelopathy, that would interfere with patient evaluation, accurate completion of the symptom scale, or compliance with subcutaneous injection.

Concurrent Medication:

Excluded:

• Chemotherapeutic agents.
• Systemic corticosteroids or immunomodulators.
• Initiation of new antiretroviral to a stable regimen.

Prior Medication:

Excluded:

• Neurotoxic systemic chemotherapy within the past 90 days.
• Systemic corticosteroids or immunomodulators within the past 30 days.
• Initiation of non-opioid prescription medication for pain during the 2 weeks preceding randomization (including tricyclic antidepressants, mexiletine, phenytoin, and carbamazepine).
• Treatment for acute opportunistic infections within the past 14 days (maintenance therapy for CMV retinitis, MAI bacteremia, or cryptococcal meningitis is permitted).

Active drug or alcohol abuse that would affect study compliance.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Masking: DOUBLE

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: McArthur J; Study Chair: Schifitto G

Publications and helpful links

General Publications

• Nerve growth factor study opens. GMHC Treat Issues. 1996 Nov;10(11):9.
• Gilden D. Hyperthermia study finds little effect. GMHC Treat Issues. 1995 Nov;9(11):5-7.
• James JS. Nerve growth factor: major trial canceled, revived after protest. AIDS Treat News. 1995 Apr 21;(no 221):5.
• Simpson DM, Haidich AB, Schifitto G, Yiannoutsos CT, Geraci AP, McArthur JC, Katzenstein DA; ACTG 291 study team. Severity of HIV-associated neuropathy is associated with plasma HIV-1 RNA levels. AIDS. 2002 Feb 15;16(3):407-12. doi: 10.1097/00002030-200202150-00012.
• Lein B. Potential therapy for painful neuropathy. PI Perspect. 1995 May;(no 16):11.
• 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, Karalnik IJ. A phase II trial of nerve growth factor for sensory neuropathy associated with HIV infection. AIDS Clinical Trials Group Team 291. Neurology. 2000 Mar 14;54(5):1080-8. doi: 10.1212/wnl.54.5.1080. Erratum In: Neurology 2000 Jul 13;55(1):162.

Study record dates

Study Major Dates

• Study Completion (ACTUAL): February 1, 1999

Study Registration Dates

• First Submitted: November 2, 1999
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (ESTIMATE): August 31, 2001

Study Record Updates

• Last Update Posted (ACTUAL): November 4, 2021
• Last Update Submitted That Met QC Criteria: October 27, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Peripheral Nervous System Diseases; Growth Substances; Nerve Growth Factors
• Additional Relevant MeSH Terms: Neuromuscular Diseases; Peripheral Nervous System Diseases; Nervous System Diseases; Molecular Mechanisms of Pharmacological Action; Mitosis Modulators; Mitogens
• Other Study ID Numbers: ACTG 291; 11267 (REGISTRY: DAIDS ES Registry Number)