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

This study has been terminated.
(The study was closed prematurely due to poor accrual.)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01111292
First received: April 24, 2010
Last updated: June 1, 2016
Last verified: June 2016
  Purpose
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.

Condition Intervention Phase
Colon Carcinoma
Dysplasia in Crohn Disease
Low Grade Dysplasia in Ulcerative Colitis
Rectal Carcinoma
Drug: Inositol
Other: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Myo-Inositol Chemoprevention in Colitis-Associated Dysplasia

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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. [ Time Frame: Baseline to 90 days ] [ Designated as safety issue: No ]
    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.


Enrollment: 5
Study Start Date: October 2010
Study Completion Date: September 2014
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: PLCB

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01111292

Locations
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637
United States, New York
Mount Sinai Medical Center
New York, New York, United States, 10029
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Seema Khan Northwestern University
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01111292     History of Changes
Other Study ID Numbers: NCI-2011-01434  NCI-2011-01434  CDR0000671302  NCI09-13-02  NWU09-13-02  P30CA060553  N01CN35157 
Study First Received: April 24, 2010
Results First Received: January 29, 2016
Last Updated: June 1, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Crohn Disease
Colitis
Colitis, Ulcerative
Hyperplasia
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Colonic Diseases
Pathologic Processes
Inositol
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 23, 2016