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

NCT ID: NCT04053621

Last Updated: 2020-10-22

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 92 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-31
• Study Completion Date: 2022-03-31

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.

Conditions

Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Thiamine pyrophosphate

Intervention Type: DIETARY_SUPPLEMENT

12 weeks of weekly dose of 1 gram of thiamine pyrophosphate administered in an intravenous manner with saline solution

Metformin

Intervention Type: DRUG

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

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

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

Metformin

Intervention Type: DRUG

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

Interventions

Thiamine pyrophosphate

12 weeks of weekly dose of 1 gram of thiamine pyrophosphate administered in an intravenous manner with saline solution

Intervention Type: DIETARY_SUPPLEMENT

Placebo

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

Intervention Type: OTHER

Metformin

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

Intervention Type: DRUG

Other Intervention Names

Cocarboxylase

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Universidad Nacional Autonoma de Mexico

OTHER

Sponsor Role: collaborator

Laboratorios Manuell SA

INDUSTRY

Sponsor Role: lead

Responsible Party

Dr. Melchor Alpízar Salazar

Principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Melchor Alpizar, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Centro Especializado en Diabetes, Obesidad, Prevención y Enfermedades Cardiovasculares, S.C.

Locations

Centro Especializado en Diabetes, Obesidad, Prevención y Enfermedades Cardiovasculares, S.C.

Mexico City, Mexico City, Mexico

Countries

Mexico

Central Contacts

Melchor Alpizar, MD, PhD

Role: CONTACT

malpizar@cedopec.com

52824343 ext. 201

Facility Contacts

Melchor Alpizar, MD, PhD

Role: primary

malpizar@cedopec.com

52824343 ext. 201

References

Alaei Shahmiri F, Soares MJ, Zhao Y, Sherriff J. High-dose thiamine supplementation improves glucose tolerance in hyperglycemic individuals: a randomized, double-blind cross-over trial. Eur J Nutr. 2013 Oct;52(7):1821-4. doi: 10.1007/s00394-013-0534-6. Epub 2013 May 29.

Reference Type: BACKGROUND

PMID: 23715873 (View on PubMed)

Al-Daghri NM, Alharbi M, Wani K, Abd-Alrahman SH, Sheshah E, Alokail MS. Biochemical changes correlated with blood thiamine and its phosphate esters levels in patients with diabetes type 1 (DMT1). Int J Clin Exp Pathol. 2015 Oct 1;8(10):13483-8. eCollection 2015.

Reference Type: BACKGROUND

PMID: 26722561 (View on PubMed)

Benítez-Rodríguez MT. Actualidades del Pirofosfato de Tiamina o Carboxilasa. 1st ed. México: Litográfica Santander; 2013.

Reference Type: BACKGROUND

Elksnis A, Martinell M, Eriksson O, Espes D. Heterogeneity of Metabolic Defects in Type 2 Diabetes and Its Relation to Reactive Oxygen Species and Alterations in Beta-Cell Mass. Front Physiol. 2019 Feb 13;10:107. doi: 10.3389/fphys.2019.00107. eCollection 2019.

Reference Type: BACKGROUND

PMID: 30837889 (View on PubMed)

Lopez-Carmona JM, Rodriguez-Moctezuma JR, Ariza-Andraca CR, Martinez-Bermudez M. [Lifestyle and metabolic control in patients with type 2 diabetes mellitus. Construct validation of IMEVID questionnaire]. Aten Primaria. 2004 Jan;33(1):20-7. doi: 10.1016/s0212-6567(04)78873-3. Spanish.

Reference Type: BACKGROUND

PMID: 14746741 (View on PubMed)

Pacal L, Kuricova K, Kankova K. Evidence for altered thiamine metabolism in diabetes: Is there a potential to oppose gluco- and lipotoxicity by rational supplementation? World J Diabetes. 2014 Jun 15;5(3):288-95. doi: 10.4239/wjd.v5.i3.288.

Reference Type: BACKGROUND

PMID: 24936250 (View on PubMed)

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.

Reference Type: BACKGROUND

Other Identifiers

2336732

Identifier Type: -

Identifier Source: org_study_id