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

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ClinicalTrials.gov Identifier: NCT04053621
Recruitment Status : Recruiting
First Posted : August 12, 2019
Last Update Posted : August 12, 2019
Sponsor:
Collaborator:
Universidad Nacional Autonoma de Mexico
Information provided by (Responsible Party):
Dr. Melchor Alpízar Salazar, Laboratorios Manuell SA

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Dietary Supplement: Thiamine pyrophosphate Other: Placebo Drug: Metformin Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 92 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Pirofosfato de Tiamina Como Coadyuvante de la Metformina en el Tratamiento de Pacientes Con Diabetes Mellitus Tipo 2
Estimated Study Start Date : August 2019
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : June 2020


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 Name: 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.

Other: Placebo
12 weeks of weekly dose of 275 ml of saline solution administered in an intravenous manner

Drug: Metformin
All participants will continue taking metformin in their previous established tolerated dose for the duration of the study




Primary Outcome Measures :
  1. hemoglobin A1c [ Time Frame: Change from baseline at 3 months ]
    percentage


Secondary Outcome Measures :
  1. fasting plasma glucose [ Time Frame: Change from baseline at 3 months ]
    mg/dl

  2. Lipids profile [ Time Frame: Change from baseline at 3 months ]
    Concentration of total cholesterol, HDL, LDL and triglycerides (mg/dl)

  3. 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

  4. 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.

  5. heart rate variability [ Time Frame: Change from baseline at 3 months ]
    measured in milliseconds

  6. arterial elasticity [ Time Frame: Change from baseline at 3 months ]
    Using the HDI/PulseWave instrument



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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): NCT04053621


Contacts
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Contact: Melchor Alpizar, MD, PhD 52824343 ext 201 malpizar@cedopec.com

Locations
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Mexico
Centro Especializado en Diabetes, Obesidad, Prevención y Enfermedades Cardiovasculares, S.C. Recruiting
Mexico City, Cdmx, Mexico, 11650
Contact: Melchor Alpizar, MD, PhD    52824343 ext 201    malpizar@cedopec.com   
Principal 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         
Sponsors and Collaborators
Laboratorios Manuell SA
Universidad Nacional Autonoma de Mexico
Investigators
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Principal Investigator: Melchor Alpizar, MD, PhD Centro Especializado en Diabetes, Obesidad, Prevención y Enfermedades Cardiovasculares, S.C.

Publications:
Benítez-Rodríguez MT. Actualidades del Pirofosfato de Tiamina o Carboxilasa. 1st ed. México: Litográfica Santander; 2013.
Shapoval GS, Babii LV, Kruglyak OS, Vovk AI. Antioxidant activity of thiamine and its structural analogs in reactions with electrochemically generated hydroxyl radicals and hydrogen peroxide. Theor Exp Chem. 2011; 47, 1: 55 - 60.

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Responsible Party: Dr. Melchor Alpízar Salazar, Principal investigator, Laboratorios Manuell SA
ClinicalTrials.gov Identifier: NCT04053621     History of Changes
Other Study ID Numbers: 2336732
First Posted: August 12, 2019    Key Record Dates
Last Update Posted: August 12, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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

Keywords provided by Dr. Melchor Alpízar Salazar, Laboratorios Manuell SA:
metformin
thiamine pyrophosphate
B1 vitamin
type 2 diabetes mellitus
metabolic pathways

Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Thiamine
Thiamine Pyrophosphate
Metformin
Pharmaceutical Solutions
Hypoglycemic Agents
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Nutrients
Growth Substances