Effect of Melatonin and Metformin on Glycemic Control Genotoxicity and Cytotoxicity Markers in Patients With Prediabetes

September 24, 2019 updated by: Lizet Yadira Rosales Rivera, University of Guadalajara

Effect of the Administration of Melatonin and Metformin on Glycemic Control, Genotoxicity and Cytotoxicity Markers in Patients With Prediabetes: Pilot Study

Melatonin is a hormone that regulates the circadian cycle in addition to having an antioxidant effect. Patients with prediabetes state, has a deregulation of glucose metabolism and an overproduction of reactive oxygen species caused by levels of hyperglycemia that generate DNA modification in pancreatic beta cells, which leads to apoptosis and a deficient production of insulin. The administration of metformin and melatonin could be a possibility to treat and reverse the prediabetic state decreasing the glycemic levels and reactive oxygen species production.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

A randomized, double blind, placebo-controlled, pilot clinical trial will carried out in 42 patients with a diagnosis of prediabetes, according to the American Diabetes Association criteria. The patients will be divide in three groups administrating metformin plus placebo, melatonin plus placebo or melatonin plus metformin. The intervention will be with 500 mg lengthed release tablets of metformin once a day in the morning, per 90 days, 5 mg lengthed release capsules of melatonin one a day in the night per 90 days and calcined magnesia as a placebo. Before and after the intervention, will be evaluate: fasting plasma glucose, blood glucose after an oral glucose tolerance test, A1c hemoglobin fraction, micronuclei frequency, nuclear anomalies frequency, insulin secretion and insulin sensitivity, weight, height, body mass index, triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, creatinine, uric acid, and sleep quality.

Study Type

Interventional

Enrollment (Anticipated)

42

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mexico
    • Jalisco
      • Guadalajara, Jalisco, Mexico, 44340
        • Recruiting
        • Institute of Experimental and Clinical Therapeutics (INTEC), CUCS, University of Guadalajara
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age beween 30 to 60 years old.
  • Diagnosis of Prediabetes state according to the American Diabetes Association criteria.
  • Without pharmacological treatment.
  • Body mass index between 25 to 34.9 Kg/m2
  • Sign informed consent

Exclusion Criteria:

  • Patients with pharmacological treatment.
  • Pregnant woman
  • Patients with autoimmune, cancer, reumatic diases history or with pharmaceutical treatment
  • Workers on night or changing shifts.
  • Subjects that have been exposed to radiation
  • Dyslipidemia: Total cholesterol >250mg/dL, Triglycerides >500 mg/dL.
  • Subjects that have travel to other place with a different time zone.
  • Patients with diagnosis of insomnia
  • Patients with a glomerular filtration <60 ml/min using the Cockroft-Gault Formula.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: melatonin plus metformin

It will be indicate metformin 850 mg tablets, once a day in the morning (before breakfast) per 90 days.

Will administrate melatonin 5 mg lengthed release capsules, once a day in the night (before bedtime) per 90 days.
Drug: melatonin
The administration of melatonin will be indicated at night before bedtime to avoid alterations of the circadian cycle. It will be contained in bottles labeled "Medication 2" to maintain the masking. This intervention will be indicated in two groups (Melatonin plus metformin and Melatonin plus placebo)
Other Names:
  • Cronocaps
Drug: metformin
For the intervention with metformin, prolonged-release tablets will be used to reduce adverse effects and improve adherence to treatment. It will be contained in bottles labeled "Medication 1" to maintain masking. This intervention will be indicated in two groups (Melatonin plus metformin and metformin plus placebo)
Other Names:
  • Ifor
Active Comparator: metformin plus placebo

It will be indicate metformin 850 mg tablets, once a day in the morning (before breakfast) per 90 days.

Will administrate homologated placebo once a day in the night (before bedtime) per 90 days.
Drug: metformin
For the intervention with metformin, prolonged-release tablets will be used to reduce adverse effects and improve adherence to treatment. It will be contained in bottles labeled "Medication 1" to maintain masking. This intervention will be indicated in two groups (Melatonin plus metformin and metformin plus placebo)
Other Names:
  • Ifor
Drug: Placebo
The placebo may be contained in bottles labeled "Medication 1" or "Medication 2" depending on the time of administration, and the group in which it is used. Placebo will be used in two groups (Melatonin plus placebo and Metformin plus placebo)
Other Names:
  • Calcined magnesia
Experimental: melatonin plus placebo

It will be indicate homologated placebo once a day in the morning (before breakfast) per 90 days.

Will administrate melatonin 5 mg lengthed release capsules, once a day in the night (before sleep) per 90 days.
Drug: melatonin
The administration of melatonin will be indicated at night before bedtime to avoid alterations of the circadian cycle. It will be contained in bottles labeled "Medication 2" to maintain the masking. This intervention will be indicated in two groups (Melatonin plus metformin and Melatonin plus placebo)
Other Names:
  • Cronocaps
Drug: Placebo
The placebo may be contained in bottles labeled "Medication 1" or "Medication 2" depending on the time of administration, and the group in which it is used. Placebo will be used in two groups (Melatonin plus placebo and Metformin plus placebo)
Other Names:
  • Calcined magnesia

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fasting plasma glucose (FPG)
Time Frame: Baseline to week 12
The FPG will be evaluate in a blood sample after a 8 - 12 hour fasting period. Will be use a fotometric quantification of glucose levels in plasma sample and will report in mg/dL.
Baseline to week 12
Blood Glucose level after an Oral Glucose tolerance Test
Time Frame: Baseline to week 12
Will estimate the glucose levels at 2 hours after administration of 75 grams of anhydrid dextrosa. The result will report in mg/dL.
Baseline to week 12
A1c Hemoglobin Fraction (HbA1C)
Time Frame: Baseline to week 12
HbA1c will be measured with High-performance liquid chromatography technique from a blood sample. The result will report in percentage (%).
Baseline to week 12
Micronuclei frequency
Time Frame: Baseline to week 12
The frequency of micronuclei will be measured from a cytological sample obtained from the oral epithelium by careful scraping of both cheeks. A fluorescence technique will be performed using acridine orange, as well as a Giemsa-Wrigth stain. The result will be reported in micronucleus frequency per 1000 cells.
Baseline to week 12
Nuclear anomalies frequency
Time Frame: Baseline to week 12
The nuclear anomalies frequency will be measured from a cytological sample obtained from the oral epithelium by careful scraping of both cheeks. A fluorescence technique will be performed using acridine orange, as well as a Giemsa-Wrigth stain. They will be divided according to their morphology (multinucleated cells, pyknotic nucleus, karyorrhexis, caryolysis, nuclei buds, condensed chromatin) and will be reported by the number of findings per 1000 cells.
Baseline to week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Body height
Time Frame: Baseline to week 12
It will be determined using the electric bioimpedance scale with electrical stadiometer. The measurement will be made with the patient standing on the marks on the bioimpedance scale, in an upright position. This determination will be reported in meters (m) with a minimum precision of 0.01 meters.
Baseline to week 12
Body weight
Time Frame: Baseline to week 12
t will be determined using the electric bioimpedance scale with electrical stadiometer. The measurement will be made with the patient standing on the marks on the bioimpedance scale, in an upright position. This determination will be reported in kilograms (Kg).
Baseline to week 12
Body mass index
Time Frame: Baseline to week 12
The calculation will be made using the results of the weight, and height. From these results will be calculated by dividing the weight obtained over the square of the height. This index will be reported in kilograms per square meter (kg / m2)
Baseline to week 12
Insulin Secretion
Time Frame: Baseline to week 12
The calculation will be made using the insulogenic index, using the values obtained in the oral glucose tolerance test, and determining the insulin levels in plasma at 120 minutes and at the baseline measurement, as well as the glucose levels obtained at the 120 minutes and at the baseline measurement.
Baseline to week 12
Baseline Insulin Secretion
Time Frame: Baseline to week 12
It will be use the Stumvoll index for the calculation of this parameter.
Baseline to week 12
Insulin sensitivity
Time Frame: Baseline to week 12
For the calculation of this parameter the Matsuda index will be used, from the values obtained and applying the formula.
Baseline to week 12
Total Cholesterol
Time Frame: Baseline to week 12
The determination of total cholesterol will be made from a blood sample with the patient fasting between 8 to 12 hours. Samples will be analyzed by spectrophotometry. The result will be reported in milligrams per deciliter (mg / dL).
Baseline to week 12
High-density lipoprotein (HDL)
Time Frame: Baseline to week 12
The determination of HDL will be made from a blood sample with the patient fasting between 8 to 12 hours. Samples will be analyzed by spectrophotometry. The result will be reported in milligrams per deciliter (mg / dL).
Baseline to week 12
Low-density lipoprotein
Time Frame: Baseline to week 12
LDL will be calculated using the Friedewald formula from the results obtained of total cholesterol, HDL and triglycerides. The result will be expressed in milligrams per deciliter (mg / dl).
Baseline to week 12
Triglycerides
Time Frame: Baseline to week 12
The determination of triglycerides will be made from a blood sample with the patient fasting between 8 to 12 hours. Samples will be analyzed by spectrophotometry. The result will be reported in milligrams per deciliter (mg / dL).
Baseline to week 12
Serum Lactate
Time Frame: Baseline to week 12
The determination of serum lactate will be made from a blood sample with the patient fasting between 8 to 12 hours. Samples will be analyzed by spectrophotometry. The result will be reported in millimoles per Liter (mg / dL).
Baseline to week 12

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sleep quality
Time Frame: Baseline to week 12
It will be determined by the Pittsburgh Sleep Quality Index (PSQI). This will be done by interviewing the patient and each of the components is scored. The result will be expressed in points, and a total score equal to or less than 5 will be taken as reference to determine a good sleep quality.
Baseline to week 12
Tolerability to treatment
Time Frame: Baseline to week 12
The patient will be instructed to record in a follow-up diary any condition, alteration or change in the state of health that could occur during the period of the intervention. In addition to this, there is the contact section where you can communicate with the investigating doctor, or protocol director to report alterations. The report of adverse effects presented as a result of the intervention will be made.
Baseline to week 12
Treatment attachment
Time Frame: Baseline to week 12
The attachment to treatment will be determined by quantifying remaining capsules in the bottle during monthly follow-up appointments. At the end of the study, the sum of all the capsules per medicine will be made and it will be classified as an adequate attachment to those that meet ≥ 80% of the doses during the 90 days of intervention.
Baseline to week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Guadalajara

Investigators

  • Principal Investigator: Lizet Yadira Rosales-Rivera, PhD Science, Instituto de Terapéutica Experimental y Clínica

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 22, 2019

Primary Completion (Anticipated)

August 1, 2021

Study Completion (Anticipated)

December 1, 2021

Study Registration Dates

First Submitted

February 15, 2019

First Submitted That Met QC Criteria

February 19, 2019

First Posted (Actual)

February 20, 2019

Study Record Updates

Last Update Posted (Actual)

September 26, 2019

Last Update Submitted That Met QC Criteria

September 24, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CT-MEL-LESM

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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