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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01111292
First received: April 24, 2010
Last updated: September 19, 2014
Last verified: August 2014
  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 Cancer
Crohn Disease-associated Dysplasia
Rectal Cancer
Ulcerative Colitis-associated Low-grade Dysplasia
Drug: inositol
Other: placebo
Other: laboratory biomarker analysis
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 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 ]
    The effects on disappearance of dysplasia in colonic biopsies will be determined as a pathological diagnosis rendered by two out of three study pathologists.

  • Reduction in p53 staining within dysplasia or in segments with prior dysplasia [ Time Frame: Baseline to day 90 ] [ Designated as safety issue: No ]
    Descriptive analysis will be provided.

  • Reduction in Ki67 staining within dysplasia or in segments with prior dysplasia [ Time Frame: Baseline to day 90 ] [ Designated as safety issue: No ]
    Descriptive analysis will be provided.

  • Reduction in mucosal apoptosis (cleaved caspase-3) within dysplasia or in segments with prior dysplasia [ Time Frame: Baseline to day 90 ] [ Designated as safety issue: No ]
    Descriptive analysis will be provided.

  • Reduction of mucosal mRNA levels of MCP-1 as determined by real time polymerase chain reaction (PCR) [ Time Frame: Baseline up to 90 days ] [ Designated as safety issue: No ]
    Descriptive analysis will be provided.

  • Reductions in mucosal mRNA levels of iNOS as determined by real time PCR [ Time Frame: Baseline up to 90 days ] [ Designated as safety issue: No ]
    Descriptive analysis will be provided.

  • Reductions in mucosal mRNA levels of Cox-2 as determined by real time PCR [ Time Frame: Baseline up to 90 days ] [ Designated as safety issue: No ]
    Descriptive analysis will be provided.

  • Adverse events in study treatment [ Time Frame: Up to 2 weeks post-treatment ] [ Designated as safety issue: Yes ]
    Identify the adverse event using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.


Estimated Enrollment: 20
Study Start Date: October 2010
Estimated 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
Other: laboratory biomarker analysis
Correlative 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

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
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
Chicago, Illinois, United States, 60637
United States, New York
Mount Sinai Medical Center
New York, New York, United States, 10029
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, P30CA060553
Study First Received: April 24, 2010
Last Updated: September 19, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on November 25, 2014