Co-administration of Thiamine Pyrophosphate and Metformin in Type 2 Diabetes

October 20, 2020 updated by: Dr. Melchor Alpízar Salazar, Laboratorios Manuell SA

Pirofosfato de Tiamina Como Coadyuvante de la Metformina en el Tratamiento de Pacientes Con Diabetes Mellitus Tipo 2

Chronic non-infectious diseases have a bigger impact and a higher prevalence every day world-wide. Among them, diabetes stands out being the number one cause of death from degenerative chronic illness in Mexico. Diabetes not only affects quality of life, it can also lead to severe complications that have a great economic impact as well as a health impact on the patient and their family. Some of the complications include liver failure and hypertension. This whole problem can be dated back to an initial hyperglycemic state that when left untreated further develops into insulin resistance, chronic inflammation, metabolic syndrome and diabetes. The purpose of this study is to stop this chain reaction that starts with every hyperglycemic patient by adding thiamine pyrophosphate to the treatment plan of patients diagnosed with type 2 diabetes that are poorly managed with metformin monotherapy. Thiamine pyrophosphate is a form of B1 vitamin that plays an important role as a coenzyme in multiple metabolic routes including the link between glycolysis and Krebs cycle, fatty acids metabolism and branched-chain amino acid metabolism. By doing so, these pathways improve their function and efficiency and thereby utilize plasma glucose. This in turn, decreases the formation of advanced glycation end products (AGEs) which prevents the formation of reactive oxygen and nitrogen species, ultimately there is also an anti-oxidative mechanism involved that improves the inflammatory state the patient is living with. Our hypothesis is that by adding thiamine pyrophosphate to the treatment of patients taking metformin, there will be important progress regarding the inflammatory and metabolic control of patients with type 2 diabetes.

The study will have a duration of approximately 4 months after the total sample is recruited. During this time, subjects will first be examined to determine their eligibility according to the pre-established criteria, in case of inclusion in the study they will sign an informed consent after reading it thoroughly and having answered all their questions. Baseline labs will be taken for every subject for future comparison. They will then be randomized into two parallel groups: an experimental group that will receive weekly infusions of saline infused with 1 gram of thiamine pyrophosphate or a placebo group that will also receive weekly infusions of pure saline. The patients as well as the doctors treating them will be blinded to the assignment of either group. This model will be carried out for a duration of 12 weeks total, during which every patient will continue their metformin treatment with their tolerated dose. There will be verification of treatment adherence by counting the metformin pills during every weekly visit. For the assessment of dependent variables there will be a visit every month with a blinded doctor. These visits will be for: physical and clinical evaluation, evaluation of adverse events, evaluation of treatment adherence and a heart rate variability study. The first and third months a questionnaire about lifestyle will be added to the visit schedule. On the third month, final lab tests will be performed. Finally, one month after completing the treatment, a final visit will be scheduled for a clinical and physical evaluation to make sure there are no problems.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

92

Phase

  • Not Applicable

Contacts and Locations

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

Study Contact

Study Locations

  • Mexico
    • Cdmx
      • Mexico City, Cdmx, Mexico, 11650
        • Centro Especializado en Diabetes, Obesidad, Prevención y Enfermedades Cardiovasculares, S.C.
        • Contact:
        • Sub-Investigator:
          • Tamara D Frydman, MD
        • Sub-Investigator:
          • Jessica Duran Trejo, MD
        • Sub-Investigator:
          • Fernanda Alpizar Sanchez, MD
        • Sub-Investigator:
          • Elio Noguera Suarez, MD
        • Sub-Investigator:
          • Carlos Jimenez Collado, MD

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • signed informed consent
  • diagnosed type 2 diabetes mellitus
  • HbA1c between 7.5 and 11%
  • monotherapy treatment with metformin at tolerated successful dose

Exclusion Criteria:

  • glomerular filtration rate <60 ml/min/1.73m2
  • cardiac o respiratory insufficiency
  • liver enzymes 3 times higher than normal parameters
  • known allergy to metformin or thiamine pyrophosphate
  • pregnancy, lactation or fertile age without a contraceptive method
  • participation in another study in the last 6 months
  • programmed surgery for the next 4 months
  • treatment with any other hypoglycemic agents

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: Experimental group

Metformin at patient´s tolerated oral dose (maximum of 2550 mg per day) and thiamine pyrophosphate (weekly dose of 1 gram administered by IV: 25 ml of thiamine pyrophosphate + 250 ml saline solution at a 60-80 drops/minute rate).

Total duration of 12 weeks.
Dietary supplement: Thiamine pyrophosphate
12 weeks of weekly dose of 1 gram of thiamine pyrophosphate administered in an intravenous manner with saline solution
Other Names:
  • Cocarboxylase
Drug: Metformin
All participants will continue taking metformin in their previous established tolerated dose for the duration of the study
Placebo Comparator: Placebo group

Metformin at patient´s tolerated oral dose (maximum of 2550 mg per day) and weekly administration of 275 ml of saline solution at a 60-80 drops/minute rate).

Total duration of 12 weeks.
Drug: Metformin
All participants will continue taking metformin in their previous established tolerated dose for the duration of the study
Other: Placebo
12 weeks of weekly dose of 275 ml of saline solution administered in an intravenous manner

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
hemoglobin A1c
Time Frame: Change from baseline at 3 months
percentage
Change from baseline at 3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
fasting plasma glucose
Time Frame: Change from baseline at 3 months
mg/dl
Change from baseline at 3 months
Lipids profile
Time Frame: Change from baseline at 3 months
Concentration of total cholesterol, HDL, LDL and triglycerides (mg/dl)
Change from baseline at 3 months
inflammation markers
Time Frame: Change from baseline at 3 months
Concentration of PCR, IL-6, TNF-alpha, nitric oxyde, superoxide dismutase, free fatty acids, catalase
Change from baseline at 3 months
Lifestyle measurement
Time Frame: Change from baseline at 3 months
IMEVID questionnaire (instrumento para medir el estilo de vida en diabéticos). Total scores are reported from 0-100. Higher scores are associated with a better lifestyle, >75 quartile is considered a good score.
Change from baseline at 3 months
heart rate variability
Time Frame: Change from baseline at 3 months
measured in milliseconds
Change from baseline at 3 months
arterial elasticity
Time Frame: Change from baseline at 3 months
Using the HDI/PulseWave instrument
Change from baseline at 3 months

Collaborators and Investigators

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

Sponsor

Laboratorios Manuell SA

Collaborators

Universidad Nacional Autonoma de Mexico

Investigators

  • Principal Investigator: Melchor Alpizar, MD, PhD, Centro Especializado en Diabetes, Obesidad, Prevención y Enfermedades Cardiovasculares, S.C.

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 (Anticipated)

January 1, 2021

Primary Completion (Anticipated)

January 1, 2022

Study Completion (Anticipated)

March 1, 2022

Study Registration Dates

First Submitted

August 6, 2019

First Submitted That Met QC Criteria

August 9, 2019

First Posted (Actual)

August 12, 2019

Study Record Updates

Last Update Posted (Actual)

October 22, 2020

Last Update Submitted That Met QC Criteria

October 20, 2020

Last Verified

October 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2336732

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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.

Yes

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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