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

Primary Purpose

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

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Inositol
Placebo
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Colon Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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in this study, she should inform her study physician immediately; if she is pregnant, she will be immediately withdrawn from the study and followed until the birth of the child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

Sites / Locations

  • Northwestern University
  • University of Chicago Comprehensive Cancer Center
  • Mount Sinai Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm I (inositol)

Arm II (placebo)

Arm Description

Beginning within 14 days after colonoscopy, patients receive inositol PO QD on days 1-14 and BID on days 15-90.

Beginning within 14 days after colonoscopy, patients receive placebo PO QD on days 1-14 and BID on days 15-90.

Outcomes

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.
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.

Secondary Outcome Measures

Full Information

First Posted
April 24, 2010
Last Updated
June 1, 2016
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01111292
Brief Title
Inositol in Preventing Colorectal Cancer in Patients With Colitis-Associated Dysplasia
Official Title
Myo-Inositol Chemoprevention in Colitis-Associated Dysplasia
Study Type
Interventional

2. Study Status

Record Verification Date
June 2016
Overall Recruitment Status
Terminated
Why Stopped
The study was closed prematurely due to poor accrual.
Study Start Date
October 2010 (undefined)
Primary Completion Date
September 2014 (Actual)
Study Completion Date
September 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colon Carcinoma, Dysplasia in Crohn Disease, Low Grade Dysplasia in Ulcerative Colitis, Rectal Carcinoma

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
5 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (inositol)
Arm Type
Experimental
Arm Description
Beginning within 14 days after colonoscopy, patients receive inositol PO QD on days 1-14 and BID on days 15-90.
Arm Title
Arm II (placebo)
Arm Type
Placebo Comparator
Arm Description
Beginning within 14 days after colonoscopy, patients receive placebo PO QD on days 1-14 and BID on days 15-90.
Intervention Type
Drug
Intervention Name(s)
Inositol
Other Intervention Name(s)
myo-Inositol
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
PLCB
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
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.
Description
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.
Time Frame
Baseline to 90 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Seema Khan
Organizational Affiliation
Northwestern University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University of Chicago Comprehensive Cancer Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Mount Sinai Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States

12. IPD Sharing Statement

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

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