Medical Treatment of Colitis in Patients With Hermansky-Pudlak Syndrome

Part of paid clinical trials in Bethesda, Maryland.

Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Study ID
NCT00514982
Phase
PHASE2
Status
Withdrawn

Conditions

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

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Mesalamine — DRUG
    5-Aminosalicylic Acid Derivative used to treat mild to moderate Ulcerative Colitis
  • Infliximab — DRUG
    Antirheumatic, Disease Modifying Gastrointestinal Agent, Miscellaneous, Monoclonal Antibody, Tumor Necrosis Factor (TNF) Blocking Agent used to treat gastrointestinal disorders.
  • Corticosteroids — DRUG
    Systemic Corticosteroid used to treat inflammatory conditions.
  • 6-Mercaptopurine — DRUG
    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.
  • Tacrolimus — DRUG
    Immunosuppressant Agent used to treat Liver, Heart, Kidney transplant, prevent host vs graft disease, severe atopic dermatitis.
  • Adalimumab — DRUG
    Antirheumatic, Monoclonal Antibody, Tumor Necrosis Factor (TNF) Blocking Agent used to treat Rheumatoid arthritis and Crohn's disease.

Study Details

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.

Key Dates

Start date
Aug 7, 2007
Status verified
Mar 2011
Primary completion
Mar 8, 2011
Completion
Mar 8, 2011

Study Design

Enrollment
0 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Other: 1/Drug #1
    Oral mesalamine will be used as initial therapy in patients who are not taking any medication or have not received any prior treatment for their IBD. Dosing will begin at 2.4 g PO QD and will be increased to 4.8 g QD within 2 weeks. Topical mesalamine (enema 4 g PR HS/BID or suppository 1 g PR HS/BID) may be added for patients with inflammation that is limited to the rectum (proctitis) or who have prominent complaints of urgency, incomplete evacuation or rectal bleeding.
  • Other: 1/Drug#2
    Add oral corticosteroids (prednisone) to mesalamine. The standard induction dose will be 40 mg/day. After 1 week of therapy, if the total SCCAI score has decreased by greater than or equal to 2 points the patient will continue on another week of therapy. If the SCCAI has not decreased by greater than or equal to 2 points (indicative of a reduction in symptoms) at one week, then the dose will be increased to 60 mg/day. Patients on either dosage will have another SCCAI assessment done a week later (2 weeks after beginning corticosteroids), and if they are found to be in remission (SCCAI less than or equal to 2), a steroid-tapering schedule will be initiated.
  • Other: 1/Drug#3
    Infliximab and 6-MP will be added to patients with a SCCAI greater than 2 at week 8. The first infusion of infliximab (5 mg/kg) will be given during that week. In addition, 6-MP will be initiated at doses of 1.0-1.5 mg/kg PO QD to reduce the incidence of infliximab antibody formation and facilitate steroid tapering (the target dose of 6-MP will be decreased accordingly if patients are found to have low TMPT levels/activity by genotypic or phenotypic testing). Also, steroids will also be rapidly tapered off at this time.
  • Other: 1/Drug#4
    Infliximab and 6-MP will be added to patients with a SCCAI greater than 2 at week 8. The first infusion of infliximab (5 mg/kg) will be given during that week. In addition, 6-MP will be initiated at doses of 1.0-1.5 mg/kg PO QD to reduce the incidence of infliximab antibody formation and facilitate steroid tapering (the target dose of 6-MP will be decreased accordingly if patients are found to have low TMPT levels/activity by genotypic or phenotypic testing). Also, steroids will also be rapidly tapered off at this time.
  • Other: 1/Drug#5
    Subjects with a SCCAI greater than 2 after 3 doses of infliximab will continue 6-MP, discontinue infliximab infusions and start adalimumab injections approximately 2 weeks after the 3rd dose of infliximab. Induction dosing will consist of a 160 Micro/g subcutaneous injection, followed by 80 Micro/g 2 weeks after.
  • Other: 1/Drug#6
    Patients who have a SCCAI greater than 2 after 2 doses of adalimumab will continue 6-MP, discontinue adalimumab, and start therapy with tacrolimus 0.01 mg/kg PO BID approximately 2 weeks after the second dose of adalimumab.

Primary Outcome Measure

To detect patterns of immune abnormalities in the colitis associated with Hermansky-Pudlak Syndrome (HPS). [ Time Frame: 60 weeks ]

Locations (1)

FacilityCityStateZIPSite coordinators
National Institutes of Health Clinical Center, 9000 Rockville PikeBethesdaMaryland20892-

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National Institutes of Health Clinical Center, 9000 Rockville Pike· Bethesda, MD

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