Nitazoxanide for the Treatment of Chronic Diarrhea in HIV Infected Children

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase

Completed

Phase 2

Phase 1

Conditions

Cryptosporidiosis

HIV Infections

Treatments

Drug: Nitazoxanide

Study type

Interventional

Funder types

NIH

Identifiers

NCT00055107

PACTG 369

10033 (Registry Identifier)

Details and patient eligibility

About

Cryptosporidium parvum (C. parvum) is a parasite that can cause chronic diarrhea and is a significant problem for HIV infected children in developing countries. C. parvum infection can be treated with the drug nitazoxanide (NTZ). However, NTZ has not been tested in HIV infected children. The purpose of this study is to test the safety of NTZ in HIV infected children who have chronic diarrhea caused by C. parvum.

Study hypothesis: Twice-daily NTZ is safe and well tolerated in HIV infected infants, children, and adolescents with chronic diarrhea caused by C. parvum infection.

Full description

C. parvum is a significant opportunistic infection in much of the developing world, where children may not have access to highly active antiretroviral therapy. There is currently no established therapy for chronic cryptosporidiosis in HIV infected children. The FDA has approved NTZ for the treatment of cryptosporidiosis diarrhea; however, there are no data on the safety and effectiveness of NTZ in HIV infected children. The purpose of this study is to evaluate the safety of different doses of NTZ in HIV infected children with chronic diarrhea caused by C. parvum.

In Step 1, participants will receive one of four different doses of NTZ. Participants will take NTZ twice a day for 56 days in either a liquid or pill form. All participants will be closely monitored for drug toxicity. There will be seven study visits; they will occur at study entry, Weeks 1, 2, 4, 6, and 8, and Day 70. Study visits will include a physical exam and blood, urine, and stool collection. Pharmacokinetic (PK) sampling will be performed during four of the study visits. PK sampling requires the participants to take their morning NTZ doses while in the clinic; participants will undergo additional blood collection either before or after taking NTZ. At the end of the 56-day study period, participants who are experiencing a positive clinical benefit from NTZ and who have had no harmful side effects may choose to continue taking NTZ for an additional 24 weeks and enter Step 2. Participants who do not continue taking NTZ after Day 56 will be followed for 2 additional weeks.

Enrollment

6 patients

Sex

All

Ages

3 months to 19 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria for Step 1:

HIV infected
Chronic diarrhea with 3 or more bowel movements per day for at least 5 days in the 2 weeks prior to study entry OR 2 or more bowel movements per day for at least 5 days in the 2 weeks prior to study entry if accompanied by dehydration
Documented presence of C. parvum oocysts in stool
Weight of 4.0 kg (8.8 lbs) or more AND less than or equal to the maximum weight for age group as specified in the study protocol
Parent or guardian willing to provide informed consent, if applicable
Willing to use acceptable forms of contraception

Exclusion Criteria for Step 1:

Inability to take liquid or tablet form of medication
Serum transaminase (ALT) and bilirubin greater than or equal to 5 times the upper limit of normal at study screening
Active M. avium intracellulare or cytomegalovirus (CMV) colitis
Active cancer
Certain medications
Pregnant or breastfeeding