To determine the frequency of complete, marked, and partial clinical responses in patients with cryptosporidiosis treated with 6 weeks of NTZ versus 21 days of placebo. To determine the safety of NTZ in subjects with cryptosporidiosis. There is no proven therapy for cryptosporidiosis in persons with AIDS. Nitazoxanide appears to be a good candidate drug for further evaluation because of its effectiveness in preclinical models, the data from early clinical trials and its safety profile. Cooperation between clinical researchers and basic scientists in clinical trials of agents for HIV infection and its complications is a high priority for the ACTG, the NIAID, and the NIH. Thus, it is important to design a clinical trial of NTZ that includes cooperation with basic scientists.

Condition	Treatment or Intervention	Phase
Cryptosporidiosis HIV Infections	Drug: Nitazoxanide	Phase II

Further Study Details: 

Expected Total Enrollment:  60

There is no proven therapy for cryptosporidiosis in persons with AIDS. Nitazoxanide appears to be a good candidate drug for further evaluation because of its effectiveness in preclinical models, the data from early clinical trials and its safety profile. Cooperation between clinical researchers and basic scientists in clinical trials of agents for HIV infection and its complications is a high priority for the ACTG, the NIAID, and the NIH. Thus, it is important to design a clinical trial of NTZ that includes cooperation with basic scientists.

Patients will be randomized to the active drug or placebo in a 2:1 ratio. Patients will be stratified by presence or absence of dual infection with microsporidiosis and screening CD4+ count (<= 50/mm3, > 50/mm3). Days 1 - 21, Arm I will receive oral NTZ and Arm II will receive NTZ placebo po bid (blinded). With the approval of the protocol chair, patients may switch to open-label NTZ after two weeks of blinded therapy if there is a clinical worsening of diarrhea due to cryptosporidiosis accompanied by either weight loss >= 5% or the requirement for intravenous fluids to maintain body weight and/or intravascular volume despite the use of appropriate antidiarrheal agents. Days 22 - 42, Arm I and Arm II will receive oral NTZ (open-label). Days 43 - 63, Arm I will begin the maintenance phase and Arm II will receive oral NTZ (open-label). On Day 63 Arm II will start the maintenance phase. In maintenance phase patients will be randomized to 1 of 2 doses of NTZ 24 weeks. Patients who are not complete or marked responders at Day 42 (Arm I) or Day 63 (Arm II) may receive a higher dose of NTZ for an additional three weeks. Patients who have a complete or marked response at the higher dose may initiate maintenance therapy. Patients who continue to have only a partial response or who fail to respond will discontinue therapy.

Ages Eligible for Study:  13 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

Patients must have:

• Documented HIV infection.
• Intestinal cryptosporidiosis.
• Willingness to undergo a 1 week washout phase of all anticryptosporidial medications and stabilization on a protocol directed, antidiarrheal regimen.
• Greater than or equal to 4 stools per day, on average, for a minimum of 21 out of 28 days prior to study entry, secondary to cryptosporidiosis.

AS PER AMENDMENT 2/10/97:

• Four or more stools per day, on average, during the 5-day screening period prior to baseline.

Exclusion Criteria

Co-existing Condition: Patients with the following symptoms and conditions are excluded:

• Inability to tolerate oral medications.
• Life expectancy less than 3 months in the opinion of the investigator.
• Active CMV colitis, C. difficile colitis, giardiasis, salmonellosis, shigellosis, campylobacteriosis, inflammatory bowel disease, diarrhea secondary to another documented intestinal pathogen, or active or uncontrolled MAC disease, defined as symptomatic MAC disease and/or a patient who is not on appropriate anti-MAC therapy in the presence of MAC disease.

NOTE:

• Patients who have been treated for MAC disease for at least 4 weeks and have resolved their symptoms may be enrolled. Patients dually infected with microsporidiosis may be randomized to the study but will not count toward the sample size.

AS PER AMENDMENT 2/10/97:

• Failure to record a minimum of four days of information on the use of antidiarrheal medication and the frequency of bowel movements in the daily diary during the screening period.
• Allergy to corn or corn products.

Concurrent Medication: Excluded:

• Need for continuing use of any medications with putative anticryptosporidial activity, including paromomycin, azithromycin, clarithromycin, spiramycin, bovine colostrum, monoclonal anticryptosporidial antibody preparations, letrazuril, atovaquone, diclazuril, octreotide and albendazole (prohibited during the acute treatment phase for patients dually infected with microsporidiosis)..

NOTE:

• Patients who develop cryptosporidiosis while taking azithromycin or clarithromycin may be enrolled as long as they have been taking those medications for at least four weeks and remain on a stable dosage.
• All antidiarrheals that are not part of the protocol directed Antidiarrheal Stabilization Regimen.
• The addition of any new antiretroviral agent or immunomodulator therapy the first 63 days on the study.

Prior Medication: Excluded:

• Treatment at any time prior with nitazoxanide.
• Addition of any new antiretroviral or increase in the dosage or current antiretrovirals within 4 weeks to study entry.

Alabama
      Univ of Alabama at Birmingham, Birmingham,  Alabama,  35294,  United States
California
      San Francisco Gen Hosp, San Francisco,  California,  941102859,  United States
      Univ of Southern California / LA County USC Med Ctr, Los Angeles,  California,  900331079,  United States
Colorado
      Univ of Colorado Health Sciences Ctr, Denver,  Colorado,  80262,  United States
Georgia
      Emory Univ, Atlanta,  Georgia,  30308,  United States
Illinois
      Cook County Hosp, Chicago,  Illinois,  60612,  United States
      Louis A Weiss Memorial Hosp, Chicago,  Illinois,  60640,  United States
Indiana
      Methodist Hosp of Indiana / Life Care Clinic, Indianapolis,  Indiana,  46202,  United States
Louisiana
      Charity Hosp / Tulane Univ Med School, New Orleans,  Louisiana,  70112,  United States
      Tulane Univ School of Medicine, New Orleans,  Louisiana,  70112,  United States
Massachusetts
      Beth Israel Deaconess - West Campus, Boston,  Massachusetts,  02215,  United States
Missouri
      St Louis Regional Hosp / St Louis Regional Med Ctr, St. Louis,  Missouri,  63112,  United States
New York
      Univ of Rochester Medical Center, Rochester,  New York,  14642,  United States
      Cornell Univ Med Ctr, New York,  New York,  10021,  United States
      SUNY / Erie County Med Ctr at Buffalo, Buffalo,  New York,  14215,  United States
Ohio
      Univ of Cincinnati, Cincinnati,  Ohio,  452670405,  United States
      Ohio State Univ Hosp Clinic, Columbus,  Ohio,  432101228,  United States
Pennsylvania
      Univ of Pennsylvania at Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States
South Carolina
      Julio Arroyo, West Columbia,  South Carolina,  29169,  United States
Texas
      Univ of Texas Galveston, Galveston,  Texas,  775550435,  United States
Washington
      Children's Hospital & Medical Center / Seattle ACTU, Seattle,  Washington,  981050371,  United States
      Univ of Washington, Seattle,  Washington,  981224304,  United States
Puerto Rico
      Univ of Puerto Rico, San Juan,  009365067,  Puerto Rico

Study chairs or principal investigators

Fichtenbaum C,  Study Chair
Soave R,  Study Chair

Study ID Numbers:  ACTG 336
Record last reviewed:  January 2003
Last Updated:  October 13, 2004
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00001081
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08