Interleukin 12 (IL-12) for the Treatment of Cryptosporidiosis in AIDS Patients

December 13, 2016 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

A Pilot, Proof-of-Concept, Dose-Escalating Trial of Recombinant Human Interleukin-12 (rhIL-12) Versus Placebo Along With Paromomycin and Azithromycin for Chronic Cryptosporidiosis in AIDS

There is no proven effective treatment for chronic diarrhea caused by the parasite Cryptosporidium in advanced AIDS. This trial will test the safety of interleukin-12 (IL-12) as part of a combination therapy for this parasite.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Cryptosporidium parvum can cause chronic diarrhea and biliary disease in people with AIDS, resulting in significant morbidity and mortality. Highly effective antiparasitic treatment for this infection is not currently available. Paromomycin and azithromycin have some efficacy and have been used in combination in a small number of patients. However, in clinical trials of this drug combination, patients remained infected with the parasite despite improvement of their symptoms.

Improving the immune system with highly active antiretroviral therapy (HAART) has been the most effective therapy described for cryptosporidiosis (chronic infection with Cryptosporidium parvum), with over 80% of patients showing improvement. However, immune reconstitution is not possible in all patients.

Interferon gamma expression is strongly associated with control of cryptosporidiosis. IL-12 stimulates interferon gamma, and IL-12 treatment has been shown to prevent cryptosporidiosis in mice. This study will evaluate IL-12 in combination with standard therapy for cryptosporidiosis in patients with AIDS.

This is a dose-escalation study. All patients will be treated with paromomycin and azithromycin. The initial group will be treated with either 110 ng/kg IL-12 (6 patients) or placebo injections (2 patients) twice a week for 4 weeks. If the initial dose is ineffective and the combination of drugs is tolerated, a second group of patients will be randomized to either 300 ng/kg IL-12 (6 patients) or placebo injections (2 patients) twice a week for 4 weeks. Patients will be evaluated for eradication of the parasite (as measured by immunofluorescence and intestinal biopsy), decreases in stool frequency, decreases in 24 hour stool volume, stimulation of intestinal Th1 cytokine production, increases in body weight, improvements in Karnofsky score, and improvements in serum alkaline phosphatase levels and transaminases (if elevated at baseline).

Study Type

Interventional

Enrollment

2

Phase

  • Phase 2
  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  • HIV infection
  • CD4 cell count < 150 cells/µl
  • Stable antiretroviral regime that includes at least two nucleotide analogues for at least 4 weeks
  • Viral load < 10,000 copies/ml
  • Chronic diarrhea, defined as three loose or watery bowel movements a day for 5 days per week over 3 weeks
  • Stool positive for Cryptosporidium and no other enteric pathogen (bacterial culture, C. difficile toxin assay, AFB stain, ova and parasite examination, and stain for microsporidia)
  • Karnofsky score >= 70
  • Acceptable methods of contraception

Exclusion Criteria:

  • Pregnant
  • Active opportunistic infection
  • History of hypersensitivity or significant intolerance to aminoglycosides, macrolide antibiotics, or colony stimulating factors
  • Requires intravenous fluids

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Principal Investigator: Arthur White, Baylor College of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 1997

Primary Completion (ACTUAL)

June 1, 2005

Study Completion (ACTUAL)

June 1, 2005

Study Registration Dates

First Submitted

April 2, 2003

First Submitted That Met QC Criteria

April 2, 2003

First Posted (ESTIMATE)

April 3, 2003

Study Record Updates

Last Update Posted (ESTIMATE)

December 14, 2016

Last Update Submitted That Met QC Criteria

December 13, 2016

Last Verified

March 1, 2003

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2R01AI041735-04A2 (NIH)
  • 5R01AI041735-05 (NIH)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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