Diabetes Mellitus, Type 2NCT04053621
Co-administration of Thiamine Pyrophosphate and Metformin in Type 2 Diabetes
A study testing Thiamine pyrophosphate and Metformin in people with Diabetes Mellitus, Type 2, run by Laboratorios Manuell SA at 1 site in Mexico.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetes Mellitus, Type 2
- What is being tested?
- Thiamine pyrophosphate and Metformin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 92 participants
- Where
- 1 siteMexico
- Study dates
- Jan 2021to Mar 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- signed informed consent
- diagnosed type 2 diabetes mellitus
- HbA1c between 7.5 and 11%
- monotherapy treatment with metformin at tolerated successful dose
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Mexico1 site
Centro Especializado en Diabetes, Obesidad, Prevención y Enfermedades Cardiovasculares, S.C.
Mexico City, Mexico City, 11650
Melchor Alpizar, MD, PhD, 52824343 ext. 201, malpizar@cedopec.com
Tamara D Frydman, MD
About this study
Official title: Pirofosfato de Tiamina Como Coadyuvante de la Metformina en el Tratamiento de Pacientes Con Diabetes Mellitus Tipo 2
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
- Being tested
- Thiamine pyrophosphate, Placebo, Metformin
- Keywords
- metformin, thiamine pyrophosphate, B1 vitamin, type 2 diabetes mellitus, metabolic pathways
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Thiamine pyrophosphateDietary supplement
Also called Cocarboxylase
12 weeks of weekly dose of 1 gram of thiamine pyrophosphate administered in an intravenous manner with saline solution
PlaceboOther
12 weeks of weekly dose of 275 ml of saline solution administered in an intravenous manner
MetforminDrug
All participants will continue taking metformin in their previous established tolerated dose for the duration of the study
| Study group | Role | What they receive |
|---|---|---|
| Experimental group | Experimental | 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. Receives: Dietary Supplement: Thiamine pyrophosphate; Drug: Metformin |
| Placebo group | Placebo comparator | 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. Receives: Other: Placebo; Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
hemoglobin A1c
percentage
Measured: Change from baseline at 3 months
Secondary outcomes (6)
fasting plasma glucose
mg/dl
Measured: Change from baseline at 3 months
Lipids profile
Concentration of total cholesterol, HDL, LDL and triglycerides (mg/dl)
Measured: Change from baseline at 3 months
inflammation markers
Concentration of PCR, IL-6, TNF-alpha, nitric oxyde, superoxide dismutase, free fatty acids, catalase
Measured: Change from baseline at 3 months
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.
Measured: Change from baseline at 3 months
heart rate variability
measured in milliseconds
Measured: Change from baseline at 3 months
arterial elasticity
Using the HDI/PulseWave instrument
Measured: Change from baseline at 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2019
- Study startJan 2021 (estimated)
- Primary completionJan 2022 (estimated)
- Study completionMar 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 92 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Laboratorios Manuell SA
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Universidad Nacional Autonoma de Mexico
- Responsible party
- Principal investigator, Dr. Melchor Alpízar Salazar, Laboratorios Manuell SA
- Investigators
- Melchor Alpizar, MD, PhD, Principal investigator, Centro Especializado en Diabetes, Obesidad, Prevención y Enfermedades Cardiovasculares, S.C.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04053621
- Sponsor's protocol ID
- 2336732
- Status last verified
- Oct 2020
- First submitted
- 6 Aug 2019
- Last updated
- 22 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 23715873Al-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.
PubMed 26722561Benítez-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.
PubMed 30837889Lopez-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.
PubMed 14746741Pacal 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.
PubMed 24936250Shapoval 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.
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pirofosfato de Tiamina Como Coadyuvante de la Metformina en el Tratamiento de Pacientes Con Diabetes Mellitus Tipo 2
- ClinicalTrials.gov ID
- NCT04053621
- Acronym / sponsor ID
- 2336732
- Conditions
- Diabetes Mellitus, Type 2
- Keywords
- metformin, thiamine pyrophosphate, B1 vitamin, type 2 diabetes mellitus, metabolic pathways
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 92 participants (estimated)
- Lead sponsor
- Laboratorios Manuell SAIndustry (pharma, biotech, devices)
- Collaborators
- Universidad Nacional Autonoma de Mexico
- Study start
- Jan 2021 (estimated)
- Primary completion
- Jan 2022 (estimated)
- Study completion
- Mar 2022 (estimated)
- First posted
- 12 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental group | Experimental | Dietary Supplement: Thiamine pyrophosphate, Drug: MetforminMetformin 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. |
| Placebo group | Placebo comparator | Other: Placebo, Drug: MetforminMetformin 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- signed informed consent
- diagnosed type 2 diabetes mellitus
- HbA1c between 7.5 and 11%
- monotherapy treatment with metformin at tolerated successful dose
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Thiamine pyrophosphateAlso: Cocarboxylase12 weeks of weekly dose of 1 gram of thiamine pyrophosphate administered in an intravenous manner with saline solution | Dietary supplement | Experimental group |
| Placebo12 weeks of weekly dose of 275 ml of saline solution administered in an intravenous manner | Other | Placebo group |
| MetforminAll participants will continue taking metformin in their previous established tolerated dose for the duration of the study | Drug | Experimental group, Placebo group |
Primary outcome
hemoglobin A1c
Time frame: Change from baseline at 3 months
percentage
6 secondary outcomes
fasting plasma glucose
Time frame: Change from baseline at 3 months
Lipids profile
Time frame: Change from baseline at 3 months
inflammation markers
Time frame: Change from baseline at 3 months
Lifestyle measurement
Time frame: Change from baseline at 3 months
heart rate variability
Time frame: Change from baseline at 3 months
arterial elasticity
Time frame: Change from baseline at 3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2020.
- Background: PubMed 23715873Alaei 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.
- Background: PubMed 26722561Al-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.
- BackgroundBenítez-Rodríguez MT. Actualidades del Pirofosfato de Tiamina o Carboxilasa. 1st ed. México: Litográfica Santander; 2013.
- Background: PubMed 30837889Elksnis 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.
- Background: PubMed 14746741Lopez-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.
- Background: PubMed 24936250Pacal 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.
- BackgroundShapoval 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.
- Individual participant dataSharing planned: No
Related trials for Diabetes Mellitus, Type 2
Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
Not yet recruiting
Impact of Endoscopic Sleeve Gastroplasty (ESG) in Obese Adults With Type 2 Diabetes (T2D)
Type 2 Diabetes Mellitus (T2D), Obesity (BMI>30)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Melchor Alpizar, MD, PhD principal investigator
Centro Especializado en Diabetes, Obesidad, Prevención y Enfermedades Cardiovasculares, S.C.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Thiamine pyrophosphate and Metformin in people with Diabetes Mellitus, Type 2, run by Laboratorios Manuell SA at 1 site in Mexico.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Melchor Alpizar, MD, PhD (52824343 ext. 201, malpizar@cedopec.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
hemoglobin A1c (time frame: Change from baseline at 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04053621, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2020.