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

PreDiabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03848533
• Other study ID #: CT-MEL-LESM
• Status: Recruiting
• Phase: Phase 2
• Start date: August 22, 2019
• Est. completion date: December 2021

Study information

• Verified date: February 2019
• Source: University of Guadalajara
• Contact: Lizet Y Rosales-Rivera, PhD Science
• Phone: 52 33 10585200
• Email: lizet.rosales[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: December 2021
• Est. primary completion date: August 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Glucose Intolerance
• PreDiabetes
• Prediabetic State

Intervention

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)
• 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)
• 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)

Locations

Country	Name	City	State
Mexico	Institute of Experimental and Clinical Therapeutics (INTEC), CUCS, University of Guadalajara	Guadalajara	Jalisco

Sponsors (1)

Lead Sponsor	Collaborator
University of Guadalajara

Country where clinical trial is conducted

Mexico, 

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* Note: There are 35 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Sleep quality	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
Other	Tolerability to treatment	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
Other	Treatment attachment	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
Primary	Fasting plasma glucose (FPG)	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
Primary	Blood Glucose level after an Oral Glucose tolerance Test	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
Primary	A1c Hemoglobin Fraction (HbA1C)	HbA1c will be measured with High-performance liquid chromatography technique from a blood sample. The result will report in percentage (%).	Baseline to week 12
Primary	Micronuclei frequency	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
Primary	Nuclear anomalies frequency	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	Body height	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
Secondary	Body weight	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
Secondary	Body mass index	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
Secondary	Insulin Secretion	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
Secondary	Baseline Insulin Secretion	It will be use the Stumvoll index for the calculation of this parameter.	Baseline to week 12
Secondary	Insulin sensitivity	For the calculation of this parameter the Matsuda index will be used, from the values obtained and applying the formula.	Baseline to week 12
Secondary	Total Cholesterol	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
Secondary	High-density lipoprotein (HDL)	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
Secondary	Low-density lipoprotein	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
Secondary	Triglycerides	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
Secondary	Serum Lactate	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