NCT00514982

Medical Treatment of Colitis in Patients With Hermansky-Pudlak Syndrome

An Observational Study of the Immunopathogenesis of and Response to Step-Up Inflammatory Bowel Disease Therapy for Hermansky-Pudlak Syndrome-Associated Colitis

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study will determine if medical treatment of colitis (inflammation of the colon resulting in loose bowel movements, rectal bleeding, and belly pain) that is used for other colitis conditions, such as Crohn's disease and ulcerative colitis, is safe and effective for treating colitis in patients with Hermansky-Pudlak syndrome (HPS). HPS is a hereditary disorder that causes albinism, visual impairment, and abnormal bleeding. Some patients also develop colitis, pulmonary fibrosis, and kidney disease. Patients with HPS and colitis who are 18 years of age or older may be eligible for this study. Participants receive treatment for their colitis symptoms with one or more of several study drugs, which include mesalamine (5-ASA), corticosteroids, infliximab and 6-mercaptopurine, adalimumab and tacrolimus. The drugs are added to the treatment plan one at a time to find the combination that works best for the individual patient. Patients who respond to one or more of the medications may continue treatment with that same combination for up to 6 months. Regular clinic visits are scheduled for blood tests, symptoms ratings questionnaires and periodic physical examinations and colonoscopies to measure the response to treatment and evaluate any side effects.

Detailed description

The primary purpose of this study is to detect patterns of immune abnormalities in the colitis associated with Hermansky-Pudlak Syndrome (HPS). Additionally we aim to document the clinical response to and tolerance of conventional inflammatory bowel disease (IBD) therapy for HPS patients with active colitis associated with Hermansky-Pudlak Syndrome (HPS). HPS is a rare autosomal recessive disorder causing dysfunctional lysosome-related organelle formation and trafficking resulting in oculocutaneous albinism and a bleeding diathesis secondary to platelet dysfunction. Associated conditions include pulmonary fibrosis, IBD, and systemic ceroid deposition. The associated IBD has been reported to occur at a higher frequency in the HPS-1 and HPS-4 subtypes compared to the prevalence of IBD in non-HPS populations. HPS IBD has clinical features of both ulcerative colitis (UC) and Crohn's disease, but histologically resembles Crohn's disease in that granulomas are commonly seen in the mucosa of the intestine. The pathogenesis of HPS IBD is not fully understood and little data beyond descriptions of the clinical and histologic manifestations have been published. Furthermore reports on treatment of the colitis in HPS patients are largely anecdotal, and our own experience suggests that many patients may be under-treated. HPS patients with active colitis will be enrolled into this prospective treatment study. Endpoints for the immunopathogenesis studies will include baseline measurements of and changes in immune cell populations, cytokine, and chemokine expression. In the blood and gut mucosa. Endpoints for the study of response to treatment will include changes in clinical, endoscopic, and histologic scores as well as the rate and severity of adverse events. Descriptive summary statistical analysis (n, mean, median, standard deviation, minimum and maximum range) and simple correlations of clinical response variables with immune parameters will be done.

Conditions

• Hermanski-Pudlak Syndrome
• Colitis
• Cytokines
• Lymphocytes
• Drug Evaluation

Interventions

Type	Name	Description
DRUG	Mesalamine	5-Aminosalicylic Acid Derivative used to treat mild to moderate Ulcerative Colitis
DRUG	Infliximab	Antirheumatic, Disease Modifying Gastrointestinal Agent, Miscellaneous, Monoclonal Antibody, Tumor Necrosis Factor (TNF) Blocking Agent used to treat gastrointestinal disorders.
DRUG	Corticosteroids	Systemic Corticosteroid used to treat inflammatory conditions.
DRUG	6-Mercaptopurine	Antineoplastic Agent, Antimetabolite, Immunosuppressant Agent used traditionally to treat Acute lymphoblastic leukemia. Unlabeled use as steroid-sparing agent for corticosteroid-dependent Crohn's disease (CD) and ulcerative colitis (UC); maintenance of remission in CD; fistulizing Crohn's disease.
DRUG	Tacrolimus	Immunosuppressant Agent used to treat Liver, Heart, Kidney transplant, prevent host vs graft disease, severe atopic dermatitis.
DRUG	Adalimumab	Antirheumatic, Monoclonal Antibody, Tumor Necrosis Factor (TNF) Blocking Agent used to treat Rheumatoid arthritis and Crohn's disease.

Timeline

• Start date: 2007-08-07
• Primary completion: 2011-03-08
• Completion: 2011-03-08
• First posted: 2007-08-10
• Last updated: 2017-07-02

Locations

1 site across 1 country: United States