Comparison of 2',3'-Dideoxyinosine (Didanosine, ddI) and Zidovudine in Therapy of Patients With the AIDS Dementia Complex

This study has been completed.
Sponsor:
Collaborators:
Bristol-Myers Squibb
Glaxo Wellcome
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000657
First received: November 2, 1999
Last updated: March 28, 2012
Last verified: March 2012
  Purpose

To compare the safety and effectiveness of orally administered didanosine (ddI) with high dose orally administered zidovudine (AZT) in patients who develop or exhibit progression of the AIDS dementia complex (ADC) and who have not previously been intolerant to AZT at doses of up to 1000 mg/day.

HIV-infected or AIDS patients may develop ADC which causes damage to the nervous system. ADC may be caused by some action of the AIDS virus on the nervous system, although similar problems can be caused by other infections because the AIDS virus lowers the body's ability to fight other infections. It is important to determine whether symptoms are due to ADC or to some other infection since treatment varies for different conditions. AZT has been shown to be beneficial to people with ADC although its effectiveness has only been studied in a small number of patients. Studies suggest that higher doses of AZT are more likely to be effective than standard doses in improving symptoms of ADC.


Condition Intervention Phase
AIDS Dementia Complex
HIV Infections
Drug: Zidovudine
Drug: Didanosine
Phase 2

Study Type: Interventional
Study Design: Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Comparison of 2',3'-Dideoxyinosine (Didanosine, ddI) and Zidovudine in Therapy of Patients With the AIDS Dementia Complex

Resource links provided by NLM:


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

Estimated Enrollment: 80
Study Completion Date: September 1992
Detailed Description:

HIV-infected or AIDS patients may develop ADC which causes damage to the nervous system. ADC may be caused by some action of the AIDS virus on the nervous system, although similar problems can be caused by other infections because the AIDS virus lowers the body's ability to fight other infections. It is important to determine whether symptoms are due to ADC or to some other infection since treatment varies for different conditions. AZT has been shown to be beneficial to people with ADC although its effectiveness has only been studied in a small number of patients. Studies suggest that higher doses of AZT are more likely to be effective than standard doses in improving symptoms of ADC.

Patients are randomly assigned to receive either oral ddI or oral AZT.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Chronic suppressive therapy for herpes simplex virus, cytomegalovirus, Candida albicans, and Salmonella.
  • Prophylactic therapy for Pneumocystis carinii pneumonia.
  • Maintenance anticonvulsant therapy following a seizure in the context of the AIDS dementia complex.
  • Isoniazid only if no acceptable alternative therapy is available.
  • Judicious use of benzodiazepines, tricyclics, and other antidepressants is allowed but a stable dose level should be obtained prior to entry and maintained throughout the trial.
  • In patients for whom it is medically necessary to initiate or alter therapy with these drugs during the initial 16 week study period, data will not be used in the study.
  • Metronidazole for single courses of therapy not to exceed 14 days within consecutive 90-day intervals, the first of which begins at the initiation of the study.
  • Erythropoietin for patients under the relevant Treatment IND.
  • Symptomatic therapies (such as analgesics, antihistamines, antiemetics, antidiarrheal agents).

Allowed but not encouraged:

  • trimethoprim /sulfamethoxazole (T/S) or other sulfonamides.

Patients must have the following:

  • Screened for other causes of dementia.
  • Stage 1, 2, or 3 AIDS dementia complex.
  • Estimated premorbid IQ of at least 70.
  • Anti-HIV antibody or HIV in blood and/or cerebrospinal fluid.
  • If prior history of positive syphilis serology, should have been treated with appropriate course of antibiotics; if not, such treatment should be administered prior to pretreatment screening.
  • Not have previously shown intolerance to zidovudine (AZT).
  • Able (or parent and/or guardian able) to provide written consent.

Allowed:

  • Basal cell carcinoma, in situ carcinoma of the cervix, Kaposi's sarcoma without evidence of visceral involvement or not requiring systemic chemotherapy.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

  • Grade 3 neuropathy, based on the Neuropathy Targeted Symptom.
  • Questionnaire, or patients with any moderate abnormality indicative of peripheral neuropathy including stocking loss of sensation (to sharp pain, light touch, or vibration), distal extremity weakness (< 4/5), or absent ankle jerks.
  • History of present or past acute or chronic pancreatitis.
  • Active, symptomatic AIDS-defining opportunistic infection and requiring any ongoing maintenance therapy for confounding neurologic disease.
  • Severe premorbid psychiatric illness including bipolar illness, schizophrenia, and electroconvulsive therapy.

Previous neurological disease unrelated to HIV infection:

  • multiple sclerosis, documented stroke, degenerative disease.
  • Patients with chronic seizure disorders or head injury will only be excluded if the condition results in functional impairment or is likely to interfere with the evaluation.
  • Concurrent or previous central nervous system infections or neoplasms as revealed by Computerized Tomography (CT) or Magnetic Resonance Imaging (MRI) scan or cerebrospinal fluid analysis (such as toxoplasmosis, primary or metastatic Central Nervous System (CNS) lymphoma, progressive multifocal leukoencephalopathy, cryptococcal or other fungal meningitis, tuberculous Central Nervous System (CNS) infections, and untreated neurosyphilis).

Concurrent Medication:

Excluded:

  • Intravenous pentamidine. DHPG (Ganciclovir) should not be co-administered.
  • Monoamine oxidase (MAO) inhibitors, phenothiazines, butyrophenones, barbiturates, amphetamines.
  • Oral acidifying agents.

Patients with the following are excluded:

  • Neoplasms not specifically allowed.
  • Grade 3 neuropathy.
  • History of present or past acute or chronic pancreatitis.
  • Active, symptomatic AIDS-defining opportunistic infection.
  • Requiring any ongoing maintenance therapy for confounding neurologic disease.
  • Conditions listed under Exclusion Co-existing Conditions.

Prior Medication:

Excluded within 30 days of study entry:

  • Anti-HIV therapy other than zidovudine (AZT).
  • Biologic response modifiers.
  • Corticosteroids.
  • Drugs toxic to peripheral nerves.
  • Investigative drugs.
  • Neurotoxic drugs.

Excluded:

  • Dideoxycytidine (ddC).

Active alcohol or drug abuse or methadone maintenance sufficient, in the investigator's opinion, to prevent adequate compliance with study therapy and evaluations.

  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: NCT00000657

Locations
United States, California
San Francisco Gen Hosp
San Francisco, California, United States, 941102859
San Francisco AIDS Clinic / San Francisco Gen Hosp
San Francisco, California, United States, 941102859
United States, Indiana
Indiana Univ Hosp
Indianapolis, Indiana, United States, 462025250
United States, Louisiana
Charity Hosp / Tulane Univ Med School
New Orleans, Louisiana, United States, 70112
Louisiana State Univ Med Ctr / Tulane Med School
New Orleans, Louisiana, United States, 70112
Tulane Univ School of Medicine
New Orleans, Louisiana, United States, 70112
United States, Maryland
Johns Hopkins Hosp
Baltimore, Maryland, United States, 21287
United States, Minnesota
Univ of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, New York
Mount Sinai Med Ctr
New York, New York, United States, 10029
Univ of Rochester Medical Center
Rochester, New York, United States, 14642
United States, North Carolina
Univ of North Carolina
Chapel Hill, North Carolina, United States, 275997215
United States, South Carolina
Julio Arroyo
West Columbia, South Carolina, United States, 29169
United States, Washington
Univ of Washington
Seattle, Washington, United States, 981224304
Sponsors and Collaborators
Bristol-Myers Squibb
Glaxo Wellcome
Investigators
Study Chair: C Hall
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000657     History of Changes
Other Study ID Numbers: ACTG 140, 11115
Study First Received: November 2, 1999
Last Updated: March 28, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Didanosine
Drug Evaluation
Drugs, Investigational
AIDS Dementia Complex
Zidovudine

Additional relevant MeSH terms:
Dementia
HIV Infections
Acquired Immunodeficiency Syndrome
AIDS Dementia Complex
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
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
Zidovudine
Didanosine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 16, 2014