Protocol for Correlating Enteropathic Severity and Small Intestinal CYP3A4 Activity in Patients With Celiac Disease

NCT01338324 | Completed Phase 2 DMC

• 1 other identifier: N-1229
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

The small bowel biopsy is the cornerstone of for the diagnosis of celiac disease. In addition to being the gold standard for the initial diagnosis of celiac disease, periodic biopsies are also recommended on an ongoing basis for this life-long disease. However, biopsy evaluation is invasive and expensive. Therefore, there is a need for simple, non-invasive tests that can be performed on celiac patients with subclinical disease. The present study is based on the hypothesis that the expression and activity of cytochrome P450 CYP3A4 in the small intestinal mucosa is a sensitive measure of enteropathy. Therefore small intestinal CYP3A4 activity will be markedly different in celiac disease patients with active disease as compared to patients in remission. Small intestinal CYP3A4 activity will be measured in three ways: (i) Cmax of oral simvastatin, a widely used drug that is predominantly metabolized by small intestinal CYP3A4; (ii) AUC of oral simvastatin; and (iii) Measurement of CYP3A4 activity in two small bowel biopsies.

Conditions

Celiac Disease

Keywords

Biomarker; Pharmacokinetics; Villous; Simvastatin; Celiac disease

Outcome Measures

Primary Outcomes (1)

• Maximum serum concentration (Cmax ) of simvastatin (20 mg, orally dosed after fasting) in subjects with celiac sprue

  12 hours

Secondary Outcomes (1)

• Duodenal level of cytochrome CYP3A4

  72 Hours

Interventions

Simvastatin DRUG

Simvastatin 20 mg single dose on day 1

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cohort A: Suspected celiac sprue patients who have:
• (i) Positive Anti-transglutaminase IgA levels.
• (ii) Either a first-degree relative with diagnosed celiac sprue or at least one of the following symptoms:
• iron deficiency, osteopenia, chronic diarrhea.
• Cohort B: Diagnosis of celiac disease confirmed by medical history,
• (i)Histology of small intestinal mucosa on small bowel biopsy and elevated serum concentrations of anti-transglutaminase antibodies.
• (ii)Followed gluten-free diet for at least 1 year.
• If the subject is female, she is eligible to enter and participate in this study if she is physiologically incapable of becoming pregnant or has a negative urine pregnancy test at screening.

You may not qualify if:

• Smoking
• Any gastrointestinal or hepatic disease besides celiac sprue.
• Clinically significant renal disease.
• Use of any prescription or non-prescription drugs (including vitamins and herbal supplements) must be discontinued 30 days prior to study.

Sponsors & Collaborators

• All India Institute of Medical Sciences: lead
• University of Zurich: collaborator

Study Sites (1)

All India Institute of Medical Sciences

New Delhi, National Capital Territory of Delhi, 110029, India

Location

MeSH Terms

Conditions

Celiac Disease

Interventions

Simvastatin

Condition Hierarchy (Ancestors)

Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Dr Govind K Makharia, MD, DM, DNB

  All India Institute of Medical Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Govind K Makharia

Study Record Dates

• First Submitted: April 6, 2011
• First Posted: April 19, 2011
• Study Start: April 1, 2010
• Primary Completion: June 1, 2011
• Study Completion: September 1, 2011
• Last Updated: December 13, 2011

Record last verified: 2011-12

Locations

IN (1)