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

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04053621
• Other study ID #: 2336732
• Status: Not yet recruiting
• Phase: N/A
• Start date: January 2021
• Est. completion date: March 2022

Study information

• Verified date: October 2020
• Source: Laboratorios Manuell SA
• Contact: Melchor Alpizar, MD, PhD
• Phone: 52824343
• Email: malpizar[@]cedopec.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 92
• Est. completion date: March 2022
• Est. primary completion date: January 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Dietary Supplement:
• Thiamine pyrophosphate
12 weeks of weekly dose of 1 gram of thiamine pyrophosphate administered in an intravenous manner with saline solution

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

Locations

Country	Name	City	State
Mexico	Centro Especializado en Diabetes, Obesidad, Prevención y Enfermedades Cardiovasculares, S.C.	Mexico City	Cdmx

Sponsors (2)

Lead Sponsor	Collaborator
Laboratorios Manuell SA	Universidad Nacional Autonoma de Mexico

Country where clinical trial is conducted

Mexico, 

References & Publications (7)

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. — View Citation

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. — View Citation

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

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. Review. — View Citation

López-Carmona JM, Rodríguez-Moctezuma JR, Ariza-Andraca CR, Martínez-Bermúdez 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. Spanish. — View Citation

Pácal L, Kuricová K, Kanková 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. Review. — View Citation

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	hemoglobin A1c	percentage	Change from baseline at 3 months
Secondary	fasting plasma glucose	mg/dl	Change from baseline at 3 months
Secondary	Lipids profile	Concentration of total cholesterol, HDL, LDL and triglycerides (mg/dl)	Change from baseline at 3 months
Secondary	inflammation markers	Concentration of PCR, IL-6, TNF-alpha, nitric oxyde, superoxide dismutase, free fatty acids, catalase	Change from baseline at 3 months
Secondary	Lifestyle measurement	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
Secondary	heart rate variability	measured in milliseconds	Change from baseline at 3 months
Secondary	arterial elasticity	Using the HDI/PulseWave instrument	Change from baseline at 3 months