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

This study has been terminated.
Sponsor:
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00057486
First received: April 2, 2003
Last updated: June 23, 2005
Last verified: March 2003
  Purpose

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.


Condition Intervention Phase
HIV Infections
Cryptosporidiosis
Drug: IL-12
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


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

Estimated Enrollment: 2
Study Start Date: September 1997
Estimated Study Completion Date: June 2002
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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00057486

Sponsors and Collaborators
Investigators
Principal Investigator: Arthur White Baylor College of Medicine
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00057486     History of Changes
Other Study ID Numbers: 2R01AI41735-04A2, 5R01AI041735-05
Study First Received: April 2, 2003
Last Updated: June 23, 2005
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Chronic Diarrhea
Interleukin 12

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Cryptosporidiosis
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
Intestinal Diseases, Parasitic
Parasitic Diseases
Protozoan Infections, Animal
Parasitic Diseases, Animal
Coccidiosis
Protozoan Infections
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Interleukin-12
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014