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

Myo-Inositol Chemoprevention in Colitis-Associated Dysplasia

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.

Study Overview

• Status: Terminated
• Conditions: Colon Carcinoma; Rectal Carcinoma; Dysplasia in Crohn Disease; Low Grade Dysplasia in Ulcerative Colitis
• Intervention / Treatment: Other: Placebo; Drug: Inositol

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: April 24, 2010
• First Submitted That Met QC Criteria: April 24, 2010
• First Posted (Estimate): April 27, 2010

Study Record Updates

• Last Update Posted (Estimate): July 12, 2016
• Last Update Submitted That Met QC Criteria: June 1, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Carcinoma; Hyperplasia; Crohn Disease; Colitis; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Inositol
• Other Study ID Numbers: NCI-2011-01434 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); P30CA060553 (U.S. NIH Grant/Contract); CDR0000671302; NCI09-13-02 (Other Identifier: Northwestern University); NWU09-13-02 (Other Identifier: DCP); N01CN35157 (U.S. NIH Grant/Contract)