search
Back to results

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

Primary Purpose

AIDS Dementia Complex, HIV Infections

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Zidovudine
Didanosine
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for AIDS Dementia Complex focused on measuring Didanosine, Drug Evaluation, Drugs, Investigational, AIDS Dementia Complex, Zidovudine

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • San Francisco AIDS Clinic / San Francisco Gen Hosp
  • San Francisco Gen Hosp
  • Indiana Univ Hosp
  • Charity Hosp / Tulane Univ Med School
  • Louisiana State Univ Med Ctr / Tulane Med School
  • Tulane Univ School of Medicine
  • Johns Hopkins Hosp
  • Univ of Minnesota
  • Mount Sinai Med Ctr
  • Univ of Rochester Medical Center
  • Univ of North Carolina
  • Julio Arroyo
  • Univ of Washington

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 26, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Bristol-Myers Squibb, Glaxo Wellcome
search

1. Study Identification

Unique Protocol Identification Number
NCT00000657
Brief Title
Comparison of 2',3'-Dideoxyinosine (Didanosine, ddI) and Zidovudine in Therapy of Patients With the AIDS Dementia Complex
Official Title
Comparison of 2',3'-Dideoxyinosine (Didanosine, ddI) and Zidovudine in Therapy of Patients With the AIDS Dementia Complex
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
September 1992 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Bristol-Myers Squibb, Glaxo Wellcome

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
AIDS Dementia Complex, HIV Infections
Keywords
Didanosine, Drug Evaluation, Drugs, Investigational, AIDS Dementia Complex, Zidovudine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Masking
Double
Enrollment
80 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Zidovudine
Intervention Type
Drug
Intervention Name(s)
Didanosine

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
C Hall
Official's Role
Study Chair
Facility Information:
Facility Name
San Francisco AIDS Clinic / San Francisco Gen Hosp
City
San Francisco
State/Province
California
ZIP/Postal Code
941102859
Country
United States
Facility Name
San Francisco Gen Hosp
City
San Francisco
State/Province
California
ZIP/Postal Code
941102859
Country
United States
Facility Name
Indiana Univ Hosp
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
462025250
Country
United States
Facility Name
Charity Hosp / Tulane Univ Med School
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Louisiana State Univ Med Ctr / Tulane Med School
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Tulane Univ School of Medicine
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Johns Hopkins Hosp
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Univ of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Mount Sinai Med Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Univ of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Univ of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
275997215
Country
United States
Facility Name
Julio Arroyo
City
West Columbia
State/Province
South Carolina
ZIP/Postal Code
29169
Country
United States
Facility Name
Univ of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
981224304
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
9110076
Citation
Brouwers P, Hendricks M, Lietzau JA, Pluda JM, Mitsuya H, Broder S, Yarchoan R. Effect of combination therapy with zidovudine and didanosine on neuropsychological functioning in patients with symptomatic HIV disease: a comparison of simultaneous and alternating regimens. AIDS. 1997 Jan;11(1):59-66. doi: 10.1097/00002030-199701000-00009.
Results Reference
background

Learn more about this trial

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

We'll reach out to this number within 24 hrs