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

Sponsor

Laboratorios Manuell SA (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT04053621

Collaborator

Universidad Nacional Autonoma de Mexico (Other)

Enrollment

Location

Arms

13.9

Anticipated Duration (Months)

6.6

Patients Per Site Per Month

Study Details

Study Description

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	N/A

Study Design

Study Type:

Interventional

Anticipated 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

Anticipated Study Start Date :

Jan 1, 2021

Anticipated Primary Completion Date :

Jan 1, 2022

Anticipated Study Completion Date :

Mar 1, 2022

Arms and Interventions

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.	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

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.

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

Outcome Measures

Primary Outcome Measures

hemoglobin A1c [Change from baseline at 3 months]
percentage

Secondary Outcome Measures

fasting plasma glucose [Change from baseline at 3 months]
mg/dl
Lipids profile [Change from baseline at 3 months]
Concentration of total cholesterol, HDL, LDL and triglycerides (mg/dl)
inflammation markers [Change from baseline at 3 months]
Concentration of PCR, IL-6, TNF-alpha, nitric oxyde, superoxide dismutase, free fatty acids, catalase
Lifestyle measurement [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.
heart rate variability [Change from baseline at 3 months]
measured in milliseconds
arterial elasticity [Change from baseline at 3 months]
Using the HDI/PulseWave instrument