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

Primary Purpose

Diabetes Mellitus, Type 2

Status
Unknown status
Phase
Not Applicable
Locations
Mexico
Study Type
Interventional
Intervention
Thiamine pyrophosphate
Placebo
Metformin
Sponsored by
Laboratorios Manuell SA
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 2 focused on measuring metformin, thiamine pyrophosphate, B1 vitamin, type 2 diabetes mellitus, metabolic pathways

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Experimental group

Placebo group

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

hemoglobin A1c
percentage

Secondary Outcome Measures

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

Full Information

First Posted
August 6, 2019
Last Updated
October 20, 2020
Sponsor
Laboratorios Manuell SA
Collaborators
Universidad Nacional Autonoma de Mexico
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1. Study Identification

Unique Protocol Identification Number
NCT04053621
Brief Title
Co-administration of Thiamine Pyrophosphate and Metformin in Type 2 Diabetes
Official Title
Pirofosfato de Tiamina Como Coadyuvante de la Metformina en el Tratamiento de Pacientes Con Diabetes Mellitus Tipo 2
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Unknown status
Study Start Date
January 2021 (Anticipated)
Primary Completion Date
January 2022 (Anticipated)
Study Completion Date
March 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Laboratorios Manuell SA
Collaborators
Universidad Nacional Autonoma de Mexico

4. Oversight

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
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2
Keywords
metformin, thiamine pyrophosphate, B1 vitamin, type 2 diabetes mellitus, metabolic pathways

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
92 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental group
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo group
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Dietary Supplement
Intervention Name(s)
Thiamine pyrophosphate
Other Intervention Name(s)
Cocarboxylase
Intervention Description
12 weeks of weekly dose of 1 gram of thiamine pyrophosphate administered in an intravenous manner with saline solution
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
12 weeks of weekly dose of 275 ml of saline solution administered in an intravenous manner
Intervention Type
Drug
Intervention Name(s)
Metformin
Intervention Description
All participants will continue taking metformin in their previous established tolerated dose for the duration of the study
Primary Outcome Measure Information:
Title
hemoglobin A1c
Description
percentage
Time Frame
Change from baseline at 3 months
Secondary Outcome Measure Information:
Title
fasting plasma glucose
Description
mg/dl
Time Frame
Change from baseline at 3 months
Title
Lipids profile
Description
Concentration of total cholesterol, HDL, LDL and triglycerides (mg/dl)
Time Frame
Change from baseline at 3 months
Title
inflammation markers
Description
Concentration of PCR, IL-6, TNF-alpha, nitric oxyde, superoxide dismutase, free fatty acids, catalase
Time Frame
Change from baseline at 3 months
Title
Lifestyle measurement
Description
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.
Time Frame
Change from baseline at 3 months
Title
heart rate variability
Description
measured in milliseconds
Time Frame
Change from baseline at 3 months
Title
arterial elasticity
Description
Using the HDI/PulseWave instrument
Time Frame
Change from baseline at 3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Melchor Alpizar, MD, PhD
Phone
52824343
Ext
201
Email
malpizar@cedopec.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Melchor Alpizar, MD, PhD
Organizational Affiliation
Centro Especializado en Diabetes, Obesidad, Prevención y Enfermedades Cardiovasculares, S.C.
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centro Especializado en Diabetes, Obesidad, Prevención y Enfermedades Cardiovasculares, S.C.
City
Mexico City
State/Province
Cdmx
ZIP/Postal Code
11650
Country
Mexico
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Melchor Alpizar, MD, PhD
Phone
52824343
Ext
201
Email
malpizar@cedopec.com
First Name & Middle Initial & Last Name & Degree
Tamara D Frydman, MD
First Name & Middle Initial & Last Name & Degree
Jessica Duran Trejo, MD
First Name & Middle Initial & Last Name & Degree
Fernanda Alpizar Sanchez, MD
First Name & Middle Initial & Last Name & Degree
Elio Noguera Suarez, MD
First Name & Middle Initial & Last Name & Degree
Carlos Jimenez Collado, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
23715873
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.
Results Reference
background
PubMed Identifier
26722561
Citation
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.
Results Reference
background
Citation
Benítez-Rodríguez MT. Actualidades del Pirofosfato de Tiamina o Carboxilasa. 1st ed. México: Litográfica Santander; 2013.
Results Reference
background
PubMed Identifier
30837889
Citation
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.
Results Reference
background
PubMed Identifier
14746741
Citation
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.
Results Reference
background
PubMed Identifier
24936250
Citation
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.
Results Reference
background
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.
Results Reference
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Co-administration of Thiamine Pyrophosphate and Metformin in Type 2 Diabetes

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