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

This study is currently recruiting participants.
Verified December 2013 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01111292
First received: April 24, 2010
Last updated: December 6, 2013
Last verified: December 2013
  Purpose

This randomized phase I trial is studying inositol to see how well it works in preventing colorectal cancer in patients with colitis-associated dysplasia. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of inositol may prevent colorectal cancer.


Condition Intervention Phase
Colon Cancer
Crohn Disease-associated Dysplasia
Rectal Cancer
Ulcerative Colitis-associated Low-grade Dysplasia
Drug: inositol
Other: placebo
Other: laboratory biomarker analysis
Other: questionnaire administration
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:
  • Change in P-β-catenin staining within areas of dysplasia as measured by immunohistochemistry (IHC) from samples obtained before and after study treatment [ Time Frame: Baseline to 90 days ] [ Designated as safety issue: No ]
    P-beta-catenin staining will be measured as percent of positive cells = counted # positively stained cells / total # cells present in the sample under consideration.


Secondary Outcome Measures:
  • Disappearance of dysplasia in previously marked areas [ Time Frame: Day 90 ] [ Designated as safety issue: No ]
  • Reduction in p53 and Ki67 staining within dysplasia or in segments with prior dysplasia [ Time Frame: Day 90 ] [ Designated as safety issue: No ]
  • Reduction in mucosal apoptosis (cleaved caspase-3) within dysplasia or in segments with prior dysplasia [ Time Frame: Day 90 ] [ Designated as safety issue: No ]
  • Reduction of mucosal mRNA levels (MCP-1, iNOS and Cox-2) as determined by real time polymerase chain reaction (PCR) [ Time Frame: Up to 90 days ] [ Designated as safety issue: No ]
  • Adverse events in study treatment [ Time Frame: Up to 2 weeks post-treatment ] [ Designated as safety issue: Yes ]
    Identify the adverse event using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.


Estimated Enrollment: 20
Study Start Date: October 2010
Estimated Primary Completion Date: June 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
Other: laboratory biomarker analysis
Correlative studies
Other: questionnaire administration
Ancillary studies
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
Other: laboratory biomarker analysis
Correlative studies
Other: questionnaire administration
Ancillary studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the effect of myo-inositol (inositol), administered for 3 months, on P-β-catenin staining in areas of low-grade dysplasia or in areas of prior low grade dysplasia in patients with colitis-induced low-grade dysplasia.

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 undergo biopsy and colonoscopy to confirm areas of discrete dysplasia. 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 by telephone at 2 weeks.

  Eligibility

Ages Eligible for Study:   18 Years and older
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/mm^3
  • Platelets > 100,000/mm^3
  • 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
  • The safety of myo-inositol during pregnancy is unknown; therefore, pregnant or lactating subjects are excluded
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01111292

Locations
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Raymond C. Bergan    312-908-5284    r-bergan@northwestem.edu   
Principal Investigator: Terrence Barrett         
University of Chicago Comprehensive Cancer Center Recruiting
Chicago, Illinois, United States, 60637-1470
Contact: Stephen B. Hanauer    773-702-1466    shanauer@medicine.bsd.uchicago.edu   
Principal Investigator: Stephen B. Hanauer         
United States, New York
Mount Sinai Medical Center Recruiting
New York, New York, United States, 10029
Contact: James F. Marion    212-861-2000    james.marion@mssm.edu   
Principal Investigator: James F. Marion         
Sponsors and Collaborators
Investigators
Principal Investigator: Terrence Barrett Northwestern University
  More Information

No publications provided

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, N01CN35157
Study First Received: April 24, 2010
Last Updated: December 6, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Colonic Neoplasms
Rectal Neoplasms
Colitis
Colitis, Ulcerative
Crohn Disease
Ulcer
Hyperplasia
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Gastroenteritis
Inflammatory Bowel Diseases
Pathologic Processes
Inositol
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 20, 2014