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Metformin Treatment for Colon Cancer (MECORA)

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ClinicalTrials.gov Identifier: NCT03359681
Recruitment Status : Not yet recruiting
First Posted : December 2, 2017
Last Update Posted : December 2, 2017
Sponsor:
Information provided by (Responsible Party):
Zealand University Hospital

Brief Summary:
This is a double-blinded placebo controlled randomized trial examining the effect of metformin in non-diabetic patients with colon cancer on cell growth, immunological and metabolic changes. Patients are randomized to receive metformin 20 days before and 10 days after surgery. Tumor samples are examined for changes in level of cell growth and the composition of tumor cells in the tumor is examined. Blood samples are assessed for immunological markers and insulin resistance is measured. Cell proliferation, migration and adhesion are also examined in vitro by adding plasma obtained from the patients to colon cancer cell lines grown in culture.

Condition or disease Intervention/treatment Phase
Colon Cancer Drug: Metformin Hydrochloride Drug: Placebo oral capsule Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Perioperative Metformin Treatment for Colon Cancer, a Randomized Trial
Estimated Study Start Date : December 2017
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: metformin hydrochloride
metformin, encapsulated tablet, 500mg 3 times a day for 30 days.
Drug: Metformin Hydrochloride
metformin 500mg three times a day 20 days before colon cancer surgery and 10 days after.
Other Name: metformin

Placebo Comparator: placebo oral capsule
placebo, encapsulated tablet, 500mg 3 times a day for 30 days.
Drug: Placebo oral capsule
placebo 500mg three times a day 20 days before colon cancer surgery and 10 days after.
Other Name: placebo




Primary Outcome Measures :
  1. Expression of Ki67 on tumor samples [ Time Frame: colonoscopy (baseline) and at time of operation (after intervention) ]
    The primary outcome is determination of the difference of the level of proliferation after the intervention (time of surgery) adjusted for the level seen at baseline (time of colonoscopy). This is done using immunohistochemical staining for Ki67 (a marker for proliferation) of biopsies from the tumor. The level of proliferation will be defined as the percentage of tumor nuclei showing Ki67 staining in a specific microscopic field counted at the invasive front.


Secondary Outcome Measures :
  1. Expression of cleaved Caspase-3 on tumor samples [ Time Frame: colonoscopy (baseline) and at time of operation (after intervention) ]
    Determination of the difference in the level of apoptosis after the intervention (time of surgery) adjusted for the level seen at colonoscopy (baseline). Measured by immunohistochemical staining of tumor samples for cleaved Caspase-3 (marker for apoptosis).

  2. immunoscore [ Time Frame: time of operation (after the tumor is removed) ]
    At time of operation biopsies from the core and from the invasive margin of the tumor will be taken. These biopsies are stained for CD3 and CD8 positive lymphocytes and the density of these are measured.

  3. immunological changes in bloodsamples [ Time Frame: At baseline, day of operation and postoperative day 1, 2 and 10. ]
    Bloodsamples are taken at time of inclusion, day of operation and postoperative day 1,2 and 10. These are analysed for immunological markers.

  4. insulin resistance [ Time Frame: At the day of surgery and postoperative day 1 and 2. ]
    Fasting levels of glucose and insulin are measured at the day of operation (before the operation) and at postoperative day 1 and 2. Insulin resistance is measured using the HOMA-score.

  5. blood glucose level [ Time Frame: 4 times a day on postoperative day 1 and 2 ]
    Blood glucose (capillary glucose) level is measured 4 times a day on postoperative day 1 and 2.

  6. Quality of recovery [ Time Frame: At baseline, postoperative day 1, 2, 10 and 30. ]
    The patients' subjective feeling of recovery is measured using the Danish version of the Quality of recovery-15 questionnaire. The questionnaire includes 15 questions with the possibility of 0 to 150 points (150 being the best possible quality of recovery)

  7. cell growth in vitro - proliferation [ Time Frame: At baseline, postoperative day 1 and 10. ]
    colon cancer cell lines will be grown in vitro in the presence of plasma from the patients. Differences in proliferation between the two groups are measured.

  8. cell growth in vitro - adhesion [ Time Frame: At baseline, postoperative day 1 and 10. ]
    colon cancer cell lines will be grown in vitro in the presence of plasma from the patients. Differences in adhesion between the two groups are measured.

  9. cell growth in vitro - invasion [ Time Frame: At baseline, postoperative day 1 and 10. ]
    colon cancer cell lines will be grown in vitro in the presence of plasma from the patients. Differences in invasion between the two groups are measured.

  10. microbiota [ Time Frame: At baseline and the day before surgery ]
    The microbiota of fecal samples will be analyzed using 16s rRNA analyses



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with adenocarcinoma of the colon planned for elective curative intended surgery at Slagelse hospital
  • Age of 18 or above
  • Must be able to understand and sign informed content
  • Sufficient amount of representative tumor material from the biopsies taken at the initial colonoscopy must be present

Exclusion Criteria:

  • Patients diagnosed with diabetes mellitus
  • Patients who are receiving or have received metformin or other oral antidiabetics
  • Impaired kidney function (eGFR < 60mL/min)
  • Severe liver disease (defined as transaminases above X 3 normal levels)
  • Participation in another pharmacological intervention trial
  • Predictable poor compliance (for instance not speaking fluent Danish, mentally impaired)
  • Presenting with metastatic disease
  • Patients undergoing neoadjuvant chemotherapy
  • Pregnancy or lactation (fertile women must have a negative serum or urine pregnancy test to participate)
  • Fertile women who do not use safe contraception during the study period.
  • Allergy to metformin or placebo

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03359681


Contacts
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Contact: Emilie P Colov, MD +45 61335122 eco@regionsjaelland.dk
Contact: Ismail Gögenur, MD, DMSc +45 47323037 igo@regionsjaelland.dk

Locations
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Denmark
Department of Surgery, Slagelse Hospital Not yet recruiting
Slagelse, Denmark, 4200
Contact: Emilie P Colov, MD    +45 61335122    eco@regionsjaelland.dk   
Sponsors and Collaborators
Zealand University Hospital
Investigators
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Principal Investigator: Emilie P Colov, MD Department of Surgery, Slagelse Hospital
  Study Documents (Full-Text)

Documents provided by Zealand University Hospital:

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Responsible Party: Zealand University Hospital
ClinicalTrials.gov Identifier: NCT03359681     History of Changes
Other Study ID Numbers: REG-096-2017
First Posted: December 2, 2017    Key Record Dates
Last Update Posted: December 2, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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Colonic Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Metformin
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Hypoglycemic Agents
Physiological Effects of Drugs