Effect of Melatonin and Metformin on Glycemic Control Genotoxicity and Cytotoxicity Markers in Patients With Prediabetes
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| ClinicalTrials.gov Identifier: NCT03848533 |
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Recruitment Status : Unknown
Verified February 2019 by Lizet Yadira Rosales Rivera, University of Guadalajara.
Recruitment status was: Recruiting
First Posted : February 20, 2019
Last Update Posted : September 26, 2019
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Sponsor:
University of Guadalajara
Information provided by (Responsible Party):
Lizet Yadira Rosales Rivera, University of Guadalajara
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Brief Summary:
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| PreDiabetes | Drug: melatonin Drug: metformin Drug: Placebo | Phase 2 |
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 (Clinical Trial) |
| Estimated Enrollment : | 42 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Masking Description: | It will be done using a sealed envelope, which will contain a letter A, B or C, and will be given to choose an envelope to the participants. The letter obtained will indicate the group to which the subject will belong during the intervention. The intervention designated for each of the groups will be unknown by the researcher and participants. |
| Primary Purpose: | Treatment |
| Official Title: | Effect of the Administration of Melatonin and Metformin on Glycemic Control, Genotoxicity and Cytotoxicity Markers in Patients With Prediabetes: Pilot Study |
| Actual Study Start Date : | August 22, 2019 |
| Estimated Primary Completion Date : | August 2021 |
| Estimated Study Completion Date : | December 2021 |
| Arm | Intervention/treatment |
|---|---|
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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 Name: 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 Name: Ifor |
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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 Name: 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 Name: 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 Name: 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 Name: Calcined magnesia |
Primary Outcome Measures :
- 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.
- 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.
- 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 (%).
- 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.
- 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.
Secondary Outcome Measures :
- 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.
- 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).
- 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)
- 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 Insulin Secretion [ Time Frame: Baseline to week 12 ]It will be use the Stumvoll index for the calculation of this parameter.
- 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.
- 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).
- 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).
- 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).
- 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).
- 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).
Other Outcome Measures:
- 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.
- 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.
- 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.
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| Ages Eligible for Study: | 30 Years to 60 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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.
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): NCT03848533
Contacts
| Contact: Lizet Y Rosales-Rivera, PhD Science | 52 33 10585200 ext 34212 | lizet.rosales@gmail.com | |
| Contact: Leo E Santacruz-Meneses, PhD Student | 52 33 10585200 ext 34212 | leosantmene90@gmail.com |
Locations
| Mexico | |
| Institute of Experimental and Clinical Therapeutics (INTEC), CUCS, University of Guadalajara | Recruiting |
| Guadalajara, Jalisco, Mexico, 44340 | |
| Contact: Lizet Yadira Rosales-Rivera, PhD Science 52+ (33) 1058-5200 ext 34211 lizet.rosales@gmail.com | |
| Contact: Esperanza Martínez, PhD Science 52+(33) 1058-5200 ext 34211 esperanzamartnezabundi@yahoo.com | |
Sponsors and Collaborators
University of Guadalajara
Investigators
| Principal Investigator: | Lizet Yadira Rosales-Rivera, PhD Science | Instituto de terapeutica experimental y clínica |
Publications:
Gamboa ML, Canales-Gómez JS, Castro Sandoval T de J. Bioavailability of Long Acting Capsules of Melatonin in Mexican Healthy Volunteers. J Bioequiv Availab. 2010 Sep 30;02(05).
| Responsible Party: | Lizet Yadira Rosales Rivera, Profesor investigador asociado C, University of Guadalajara |
| ClinicalTrials.gov Identifier: | NCT03848533 |
| Other Study ID Numbers: |
CT-MEL-LESM |
| First Posted: | February 20, 2019 Key Record Dates |
| Last Update Posted: | September 26, 2019 |
| Last Verified: | February 2019 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| 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 |
Keywords provided by Lizet Yadira Rosales Rivera, University of Guadalajara:
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Melatonin Metformin Pre Diabetes PreDiabetes |
Micronuclei Genotoxicity Markers Cytotoxicity Markers |
Additional relevant MeSH terms:
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Prediabetic State Glucose Intolerance Diabetes Mellitus Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Hyperglycemia Metformin |
Melatonin Hypoglycemic Agents Physiological Effects of Drugs Antioxidants Molecular Mechanisms of Pharmacological Action Protective Agents Central Nervous System Depressants |