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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000842
• Other study ID #: ACTG 291
• Secondary ID: 11267
• Status: Completed
• Phase: Phase 2
• Est. completion date: February 1999

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 270
• Est. completion date: February 1999
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• HIV Infections
• Nervous System Diseases
• Peripheral Nervous System Disease
• Peripheral Nervous System Diseases

Intervention

Drug:
• Nerve Growth Factor, Recombinant Human

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (6)

Gilden D. Hyperthermia study finds little effect. GMHC Treat Issues. 1995 Nov;9(11):5-7. — View Citation

James JS. Nerve growth factor: major trial canceled, revived after protest. AIDS Treat News. 1995 Apr 21;(no 221):5. — View Citation

Lein B. Potential therapy for painful neuropathy. PI Perspect. 1995 May;(no 16):11. — View Citation

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. Erratum in: Neurology 2000 Jul 13;55(1):162. — View Citation

Nerve growth factor study opens. GMHC Treat Issues. 1996 Nov;10(11):9. — View Citation

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. — View Citation