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

NCT03848533 | Unknown Phase 2 DMC

• 1 other identifier: CT-MEL-LESM
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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.

Conditions

PreDiabetes

Keywords

Melatonin; Metformin; Pre Diabetes; PreDiabetes; Micronuclei; Genotoxicity Markers; Cytotoxicity Markers

Outcome Measures

Primary Outcomes (5)

• 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

• 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

• 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

• 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

• 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 Outcomes (11)

• Body height

  Baseline to week 12

• Body weight

  Baseline to week 12

• Body mass index

  Baseline to week 12

• Insulin Secretion

  Baseline to week 12

• Baseline Insulin Secretion

  Baseline to week 12

Other Outcomes (3)

• Sleep quality

  Baseline to week 12

• Tolerability to treatment

  Baseline to week 12

• Treatment attachment

  Baseline to week 12

Study Arms (3)

melatonin plus metformin

EXPERIMENTAL

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; Drug: metformin

metformin plus placebo

ACTIVE COMPARATOR

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; Drug: Placebo

melatonin plus placebo

EXPERIMENTAL

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; Drug: Placebo

Interventions

melatonin DRUG

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)

Also known as: Cronocaps

melatonin plus metformin; melatonin plus placebo

metformin DRUG

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)

Also known as: Ifor

melatonin plus metformin; metformin plus placebo

Placebo DRUG

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)

Also known as: Calcined magnesia

melatonin plus placebo; metformin plus placebo

Eligibility Criteria

• Age: 30 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Guadalajara: lead

Study Sites (1)

Institute of Experimental and Clinical Therapeutics (INTEC), CUCS, University of Guadalajara

Guadalajara, Jalisco, 44340, Mexico

RECRUITING

Related Publications (35)

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MeSH Terms

Conditions

Prediabetic State; Glucose Intolerance

Interventions

Melatonin; Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperglycemia

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Lizet Yadira Rosales-Rivera, PhD Science

  Instituto de terapeutica experimental y clínica

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lizet Y Rosales-Rivera, PhD Science

CONTACT

52 33 10585200; lizet.rosales@gmail.com

Leo E Santacruz-Meneses, PhD Student

CONTACT

52 33 10585200; leosantmene90@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Profesor investigador asociado C

Study Record Dates

• First Submitted: February 15, 2019
• First Posted: February 20, 2019
• Study Start: August 22, 2019
• Primary Completion: August 1, 2021
• Study Completion: December 1, 2021
• Last Updated: September 26, 2019

Record last verified: 2019-02

Locations

ME (1)