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Metformin Hydrochloride in Preventing Esophageal Cancer in Patients With Barrett Esophagus

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01447927
Recruitment Status : Completed
First Posted : October 6, 2011
Results First Posted : July 21, 2014
Last Update Posted : July 21, 2014
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Conditions Barrett Esophagus
Esophageal Cancer
Interventions Drug: metformin hydrochloride
Other: placebo
Enrollment 93
Recruitment Details Ninety-three subjects were pre-registered through 12 Cancer Prevention Network (CPN) member organizations from February 2012 and January 2013.
Pre-assignment Details One subject withdrew post-randomization and did not receive any treatment and 18 subjects were excluded from the trial before assignment to groups: 8 out of range lab values, 4 high grade dysplasia/esophagitis/esophageal stricture, 2 intestinal metaplasia on <25% of biopsies, and 4 other reasons.
Arm/Group Title Metformin Placebo
Hide Arm/Group Description Patients receive extended-release metformin hydrochloride orally (PO) once daily (QD) on week 1, and twice daily (BID) on weeks 2-12 (every morning (QAM) every evening (QPM) on week 3) in the absence of unacceptable toxicity or disease progression. Patients receive extended-release placebo orally (PO) once daily (QD) on week 1and BID on weeks 2-12 (every morning (QAM) and every evening (QPM) on week 3) in the absence of unacceptable toxicity or disease progression.
Period Title: Overall Study
Started 38 36
Completed 33 33
Not Completed 5 3
Reason Not Completed
Adverse Event             4             3
Withdrawal by Subject             1             0
Arm/Group Title Metformin Placebo Total
Hide Arm/Group Description Patients receive extended-release metformin hydrochloride PO QD on week 1, and BID on weeks 2-12 (QAM QPM on week 3) in the absence of unacceptable toxicity or disease progression. Patients receive extended-release placebo PO QD on week 1and BID on weeks 2-12 (QAM and QPM on week 3) in the absence of unacceptable toxicity or disease progression. Total of all reporting groups
Overall Number of Baseline Participants 38 36 74
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 38 participants 36 participants 74 participants
60.5
(20.0 to 81.0)
60.5
(39.0 to 79.0)
60.5
(20.0 to 81.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 38 participants 36 participants 74 participants
Female
8
  21.1%
8
  22.2%
16
  21.6%
Male
30
  78.9%
28
  77.8%
58
  78.4%
Performance Score   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 38 participants 36 participants 74 participants
0-Fully active 37 35 72
1-Ambulatory, restricted strenuous activity 1 1 2
[1]
Measure Description: Classifies patients according to their functional impairment. Scores range from 0 (fully active) to 5 (death).
Body Mass Index  
Median (Full Range)
Unit of measure:  Kg/m^2
Number Analyzed 38 participants 36 participants 74 participants
30.1
(22.3 to 44.5)
29.9
(20.2 to 52.0)
30.0
(20.2 to 52.0)
Length of Barrett's segment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 38 participants 36 participants 74 participants
<5 cm of circumferential involvement 11 11 22
>=5 cm of circumferential involvement 27 25 52
Non-steroidal anti-inflammatory drug (NSAID) use  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 38 participants 36 participants 74 participants
Regular Use 9 8 17
No Regular Use 29 28 57
1.Primary Outcome
Title Percent Change in Median pS6K1 Immunostaining Among Participants With Barrett Esophagus
Hide Description The percent change in pS6K1 was calculated as month 3 pS6k1 values minus baseline pS6k1 values, then divide by baseline pS6k1 values and multiply by 100.
Time Frame Baseline to 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants were considered evaluable for primary endpoint if pS6K1 data were available from both the pre- and post-intervention evaluations based on the intent-to-treat principle.
Arm/Group Title Metformin Placebo
Hide Arm/Group Description:
Patients receive extended-release metformin hydrochloride PO QD on week 1, and BID on weeks 2-12 (QAM QPM on week 3) in the absence of unacceptable toxicity or disease progression.
Patients receive extended-release placebo PO QD on week 1and BID on weeks 2-12 (QAM and QPM on week 3) in the absence of unacceptable toxicity or disease progression.
Overall Number of Participants Analyzed 36 33
Median (Full Range)
Unit of Measure: percentage of change
1.4
(-88.1 to 694.0)
-14.7
(-97.7 to 1646.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin, Placebo
Comments The null hypothesis was that the percent change in mean pS6K1 values (from pre to post) was the same or increased for the metformin arm as compared to placebo. Assuming equal standard deviations (i.e. 50%) across the metformin and placebo groups, 30 participants per arm yielded 84% power to detect at least a 35% decrease in the metformin arm as compared to placebo, using a 1-sided t-test with a significant level of 0.05.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7981
Comments [Not Specified]
Method Wilcoxon Rank-Rum Test (1-sided)
Comments [Not Specified]
2.Secondary Outcome
Title Overall Adverse Event Rates
Hide Description

Number of patients that experienced adverse events (grade 1 or above) as measured by NCI CTCAE (Common Terminology Criteria for Adverse Events) v. 4.0.

The data reported in the table include only the commonly occurring adverse events (3 or more events).

Time Frame Up to 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Metformin Placebo
Hide Arm/Group Description:
Patients receive extended-release metformin hydrochloride PO QD on week 1, and BID on weeks 2-12 (QAM QPM on week 3) in the absence of unacceptable toxicity or disease progression.
Patients receive extended-release placebo PO QD on week 1and BID on weeks 2-12 (QAM and QPM on week 3) in the absence of unacceptable toxicity or disease progression.
Overall Number of Participants Analyzed 38 36
Measure Type: Number
Unit of Measure: participants
Abdominal Pain 6 0
Cough 0 3
Diarrhea 10 5
Dyspepsia 2 3
Fatigue 4 1
Flatulence 2 2
Flu like symptoms 1 2
Gastrointestinal disorders - other, specify 2 2
Headache 3 2
Nausea 5 3
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Metformin
Hide Arm/Group Description Patients receive extended-release placebo PO QD on week 1and BID on weeks 2-12 (QAM and QPM on week 3) in the absence of unacceptable toxicity or disease progression. Patients receive extended-release metformin hydrochloride PO QD on week 1, and BID on weeks 2-12 (QAM QPM on week 3) in the absence of unacceptable toxicity or disease progression.
All-Cause Mortality
Placebo Metformin
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Placebo Metformin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/36 (0.00%)      1/38 (2.63%)    
Nervous system disorders     
Amnesia  1  0/36 (0.00%)  0 1/38 (2.63%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAEV4.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Placebo Metformin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   23/36 (63.89%)      26/38 (68.42%)    
Blood and lymphatic system disorders     
Anemia  1  1/36 (2.78%)  1 1/38 (2.63%)  1
Blood and lymphatic system disorders - Other, specify  1  1/36 (2.78%)  2 0/38 (0.00%)  0
Gastrointestinal disorders     
Abdominal distension  1  1/36 (2.78%)  1 0/38 (0.00%)  0
Abdominal pain  1  0/36 (0.00%)  0 6/38 (15.79%)  6
Bloating  1  0/36 (0.00%)  0 1/38 (2.63%)  1
Diarrhea  1  5/36 (13.89%)  7 10/38 (26.32%)  12
Dry mouth  1  1/36 (2.78%)  1 1/38 (2.63%)  1
Dyspepsia  1  3/36 (8.33%)  3 2/38 (5.26%)  2
Dysphagia  1  0/36 (0.00%)  0 1/38 (2.63%)  1
Flatulence  1  2/36 (5.56%)  2 2/38 (5.26%)  2
Gastric ulcer  1  0/36 (0.00%)  0 1/38 (2.63%)  1
Gastroesophageal reflux disease  1  0/36 (0.00%)  0 2/38 (5.26%)  2
Gastrointestinal disorders - Other, specify  1  2/36 (5.56%)  2 2/38 (5.26%)  2
Gastrointestinal pain  1  0/36 (0.00%)  0 1/38 (2.63%)  1
Hemorrhoidal hemorrhage  1  1/36 (2.78%)  1 0/38 (0.00%)  0
Nausea  1  3/36 (8.33%)  3 5/38 (13.16%)  6
Oral pain  1  0/36 (0.00%)  0 1/38 (2.63%)  1
Periodontal disease  1  0/36 (0.00%)  0 1/38 (2.63%)  1
Stomach pain  1  0/36 (0.00%)  0 1/38 (2.63%)  1
Vomiting  1  2/36 (5.56%)  2 0/38 (0.00%)  0
General disorders     
Chills  1  1/36 (2.78%)  1 0/38 (0.00%)  0
Fatigue  1  1/36 (2.78%)  1 3/38 (7.89%)  4
Flu like symptoms  1  2/36 (5.56%)  2 1/38 (2.63%)  1
Localized edema  1  1/36 (2.78%)  1 0/38 (0.00%)  0
Immune system disorders     
Allergic reaction  1  1/36 (2.78%)  1 0/38 (0.00%)  0
Infections and infestations     
Sinusitis  1  1/36 (2.78%)  1 0/38 (0.00%)  0
Tooth infection  1  0/36 (0.00%)  0 1/38 (2.63%)  1
Upper respiratory infection  1  1/36 (2.78%)  1 1/38 (2.63%)  1
Investigations     
Creatinine increased  1  0/36 (0.00%)  0 1/38 (2.63%)  1
Weight loss  1  0/36 (0.00%)  0 1/38 (2.63%)  1
Metabolism and nutrition disorders     
Dehydration  1  0/36 (0.00%)  0 1/38 (2.63%)  1
Hyperglycemia  1  1/36 (2.78%)  1 0/38 (0.00%)  0
Metabolism and nutrition disorders - Other, specify  1  0/36 (0.00%)  0 1/38 (2.63%)  1
Musculoskeletal and connective tissue disorders     
Back pain  1  0/36 (0.00%)  0 1/38 (2.63%)  1
Muscle weakness lower limb  1  1/36 (2.78%)  1 0/38 (0.00%)  0
Musculoskeletal and connective tissue disorder - Other, specify  1  1/36 (2.78%)  2 0/38 (0.00%)  0
Myositis  1  0/36 (0.00%)  0 1/38 (2.63%)  1
Pain in extremity  1  1/36 (2.78%)  1 0/38 (0.00%)  0
Nervous system disorders     
Dizziness  1  1/36 (2.78%)  1 1/38 (2.63%)  1
Dysarthria  1  0/36 (0.00%)  0 1/38 (2.63%)  1
Dysgeusia  1  0/36 (0.00%)  0 1/38 (2.63%)  1
Headache  1  2/36 (5.56%)  2 3/38 (7.89%)  3
Lethargy  1  0/36 (0.00%)  0 1/38 (2.63%)  1
Nervous system disorders - Other, specify  1  0/36 (0.00%)  0 1/38 (2.63%)  1
Syncope  1  1/36 (2.78%)  1 0/38 (0.00%)  0
Psychiatric disorders     
Agitation  1  0/36 (0.00%)  0 1/38 (2.63%)  1
Insomnia  1  0/36 (0.00%)  0 2/38 (5.26%)  2
Renal and urinary disorders     
Hematuria  1  0/36 (0.00%)  0 1/38 (2.63%)  1
Respiratory, thoracic and mediastinal disorders     
Cough  1  3/36 (8.33%)  3 0/38 (0.00%)  0
Laryngeal mucositis  1  1/36 (2.78%)  1 0/38 (0.00%)  0
Sore throat  1  1/36 (2.78%)  1 1/38 (2.63%)  1
Skin and subcutaneous tissue disorders     
Skin and subcutaneous tissue disorders - Other, specify  1  1/36 (2.78%)  1 0/38 (0.00%)  0
Surgical and medical procedures     
Surgical and medical procedures - Other, specify  1  0/36 (0.00%)  0 1/38 (2.63%)  1
Vascular disorders     
Flushing  1  1/36 (2.78%)  1 0/38 (0.00%)  0
Hypertension  1  0/36 (0.00%)  0 1/38 (2.63%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAEV4.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Amitabh Chak
Organization: University Hospitals of Cleveland, Case Medical Center
Phone: 216-844-5385
EMail: Amitabh.chak@case.edu
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01447927    
Other Study ID Numbers: NCI-2011-03451
MAY10-15-03
MAYO-MAY10-15-03
CDR0000698069
First Submitted: October 5, 2011
First Posted: October 6, 2011
Results First Submitted: April 2, 2014
Results First Posted: July 21, 2014
Last Update Posted: July 21, 2014