Inositol in Preventing Colorectal Cancer in Patients With Colitis-Associated Dysplasia

Study Overview
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Brief Summary
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This pilot, randomized phase I/II trial studies how well inositol works in preventing colorectal cancer in patients with abnormal cells (dysplasia) associated with inflammation of the colon (colitis). Patients with colitis-associated dysplasia may have an increased risk of developing colorectal cancer. Inositol is a vitamin-like substance that may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate the effect of myo-inositol (inositol), administered for 3 months, on phospho (P)-beta (B)-catenin staining in areas of low-grade dysplasia or in areas of prior low grade dysplasia in subjects with known colitis-induced low grade dysplasia at baseline. SECONDARY OBJECTIVES: I. To examine the effect of myo-inositol on regression of dysplasia. II. To examine the effect of inositol on p53 and Ki67 staining within remaining dysplasia. III. To examine the effect of inositol on epithelial apoptosis (cleaved caspase-3) within dysplasia. IV. To examine the effect of inositol on reductions in mucosal messenger ribonucleic acid (mRNA) levels of monocyte chemotactic protein 1 (MCP1), inducible nitric oxide synthase (iNOS), and cyclooxygenase (Cox)-2. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Beginning within 14 days after colonoscopy, patients receive inositol orally (PO) once daily (QD) on days 1-14 and twice daily (BID) on days 15-90. ARM II: Beginning within 14 days after colonoscopy, patients receive placebo PO QD on days 1-14 and BID on days 15-90. After completion of treatment, patients undergo biopsy and colonoscopy with or without mucosal resection. After completion of study treatment, patients are followed up at 2 weeks.

Official Title
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Myo-Inositol Chemoprevention in Colitis-Associated Dysplasia

Conditions
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Colon Carcinoma, Dysplasia in Crohn Disease, Low Grade Dysplasia in Ulcerative Colitis, Rectal Carcinoma

Intervention / Treatment
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* Drug: Inositol
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have ulcerative colitis or Crohn's disease with low grade dysplasia or polyploid dysplasia or have a history of dysplasia and increased positive beta-catenin levels confirmed by a consensus of the study pathologists (2 of 2, or 2 of 3) Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Absolute neutrophil count (ANC) > 1,500/uL Platelets > 100,000/uL Total bilirubin within normal institutional limits Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT]/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT] =< 1.5 times upper limit of normal Creatinine within normal institutional limits International normalized ratio (INR) < 1.5 Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from the time of baseline pregnancy test, throughout the duration of the study, and for 1 month following cessation of study drug; females must begin adequate contraception immediately following screening pregnancy test; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately; if she is pregnant, she will be immediately withdrawn from the study and followed until the birth of the child Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Subjects with life-threatening medical conditions that would preclude study treatment intervention and colonoscopy Participants may not be receiving any other investigational agents History of allergic reactions to rice or compounds of similar chemical or biologic composition to myo-inositol (i.e., urticaria, dermatologic reaction) Use of medications known to elevate serum blood glucose; participants on steroids are still eligible, as they will be monitored weekly for fasting blood glucose Participants with dysplasia-associated lesion or mass (DALM), high-grade dysplasia or invasive colonic carcinoma are excluded Uncontrolled intercurrent illness including, but not limited to Ongoing or active infection Symptomatic congestive heart failure Unstable angina pectoris Cardiac arrhythmia Chronic renal failure Chronic renal insufficiency Psychiatric illness or social situations that would limit compliance with study requirements Prior treatment with myo-inositol History of systemic chemotherapy within 18 months of screening Subjects taking valproic acid and/or lithium Diabetes mellitus History of total proctocolectomy Concomitant primary sclerosing cholangitis (PSC) Pregnant or lactating subjects are excluded

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (inositol)<br>Beginning within 14 days after colonoscopy, patients receive inositol PO QD on days 1-14 and BID on days 15-90. | Drug: Inositol<br>* Given PO<br>* Other names: myo-Inositol;|
| Placebo Comparator: Arm II (placebo)<br>Beginning within 14 days after colonoscopy, patients receive placebo PO QD on days 1-14 and BID on days 15-90. | Other: Placebo<br>* Given PO<br>* Other names: PLCB;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Effect of Myo-inositol (Inositol) on P-β-catenin Staining in Areas of Low Grade Dysplasia in Subjects With Known Colitis-induced Low Grade Dysplasia. | The primary objective of this study will be to evaluate the effect of myo-inositol (inositol), administered for three months, on P-β-catenin staining in areas of low grade dysplasia or in areas of prior low grade dysplasia in subjects with known colitis-induced low grade dysplasia at baseline. | Baseline to 90 days |