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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000842
First received: November 2, 1999
Last updated: May 9, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
HIV Infections
Peripheral Nervous System Disease
Drug: Nerve Growth Factor, Recombinant Human
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Phase II, Double-Blind Trial of Recombinant Human Nerve Growth Factor for Treatment of HIV-Associated Sensory Neuropathy

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 270
Study Completion Date: February 1999
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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000842

Locations
United States, California
UCLA CARE Center CRS
Los Angeles, California, United States, 90095
San Mateo County AIDS Program
San Mateo, California, United States
Stanford CRS
Stanford, California, United States, 943055107
United States, Illinois
Northwestern University CRS
Chicago, Illinois, United States, 60611
United States, Maryland
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Beth Israel Deaconess - East Campus A0102 CRS
Boston, Massachusetts, United States, 02215
United States, Missouri
Washington U CRS
St. Louis, Missouri, United States
United States, New York
NY Univ. HIV/AIDS CRS
New York, New York, United States, 10016
Cornell University A2201
New York, New York, United States
Univ. of Rochester ACTG CRS
Rochester, New York, United States, 14642
United States, North Carolina
Unc Aids Crs
Chapel Hill, North Carolina, United States, 275997215
United States, Ohio
Case CRS
Cleveland, Ohio, United States, 44106
The Ohio State Univ. AIDS CRS
Columbus, Ohio, United States, 432101228
United States, Washington
University of Washington AIDS CRS
Seattle, Washington, United States, 981224304
Sponsors and Collaborators
Investigators
Study Chair: McArthur J
Study Chair: Simpson D
Study Chair: Schifitto G
  More Information

Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000842     History of Changes
Other Study ID Numbers: ACTG 291, 11267
Study First Received: November 2, 1999
Last Updated: May 9, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Peripheral Nervous System Diseases
Nerve Growth Factors
Growth Substances

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Nervous System Diseases
Peripheral Nervous System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Neuromuscular Diseases
Mitogens
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 21, 2014