Effect of Cassia Cinnamon on Arterial Stiffness Parameters in Patients With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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Type 2 diabetes mellitus is considered a serious public health problem that has been raising worldwide. In Mexico, it is an important cause of morbi - mortality and it´s characterized by hyperglycemia that promotes an increase of cardiovascular risk through the impairment of arterial stiffness and endothelial function, which, in a chronic manner promotes the development of micro and macrovascular complications. Many nutraceuticals have been currently implemented aimed to improve glycemic control, and reduce cardiovascular risk and it´s complications, which results in a better quality of life in patients with type 2 diabetes mellitus. Cassia cinnamon pulverized bark has demonstrated to have vasodilator effect independent of endothelial mechanisms, probably regulating calcium influx or release into or within the cell, the later demonstrated in mice.

Detailed Description
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A randomized, placebo control group, double blind clinical trial. 30 patients (male or female) from 40 to 65 years old with type 2 diabetes mellitus, less than 1 year of diagnosis, taking Metformin 850 mg daily, referred to the Experimental and Clinical Therapeutic Institute will be included. All patients should give written informed consent prior to be enrolled. The protocol was previously approved by the local ethics committee (Experimental and Clinical Therapeutic Institute) of University of Guadalajara, registration number: CEI/489/2019. Patients with other medical conditions, taking additional drugs or with more than 1 year of evolution will be excluded. Procedure: The entire study consists of a total of 5 visits, the first one (day - 7) is the screening visit where written informed consent, clinical history, anthropometric measurements and blood samples will be performed. The second or initial visit (day 0) consists of review of laboratory results, hemodynamic studies (i.e brachial - ankle pulse wave velocity and index for arterial stiffness and flow mediated dilation on brachial artery for endothelial function with VP1000 and UNEX EF devices respectively), and after randomization, start of intervention (either cassia cinnamon or placebo). The third and fourth visits (day 30 and 60) consist of evaluation of treatment adherence, side effects, blood tests, treatment renewal and general recommendations. The fifth and last visit (day 90) is similar to day 0 plus evaluation of treatment adherence and side effects. This is the end of intervention period.

Official Title
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Effect of Cassia Cinnamon on Arterial Stiffness Parameters in Patients With Type 2 Diabetes Mellitus

Conditions
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Arterial Stiffness

Intervention / Treatment
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* Dietary Supplement: Cassia Cinnamon
* Other: Calcined magnesia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent prior to the beginning of enrollment Men and women 40 to 65 years old Diagnosis of type 2 diabetes mellitus according to the American Diabetes Association criteria Fasting plasma glucose ≥ 126 mg/dl (7.0 mmol/L) at least 8 h of fasting Plasma glucose ≥ 200 mg/dl (11.1 mmol/L) 2 hours after oral glucose tolerance test HbA1c ≥ 6.5 % (48 mmol/mol) Plasma glucose ≥ 200 mg/dl (11.1 mmol/L) in a random glucose test with typical symptoms of hyperglucemia or hyperglycemic crisis. Exclusion Criteria: HbA1c < 6.5 % or > 10 % or fasting glucose plasma > 250 mg/dl Total serum cholesterol ≥ 240 mg/dl Triglycerides ≥ 400 mg/dl History of allergy to any of the components used in the study Consumption of additional drugs with known effects on glucose and lipids metabolism and weight reduction History of cardiovascular disease, blood abnormalities and/or kidney, pancreatic or thyroid disease Childbearing and breastfeeding women History of smoking within 12 months prior to beginning of study History of drug abuse and alcoholism Pacemaker bearing or any other permanent bioelectronic device that could modify or interfere with electrical bioimpedance tests

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel, randomized, double blind, with control group. The study consists in two groups assigned to take either cassia cinnamon or placebo. Both groups will be taken Metformin as first line therapy for type 2 diabetes mellitus
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cassia Cinnamon<br>Cassia cinnamon, capsule of 1 gram each, taken every 8 hours before meals for 90 days. | Dietary Supplement: Cassia Cinnamon<br>* Reddish - brown to light brown, typical sweet and aromatic free flowing powder.<br>|
| Placebo Comparator: Calcined Magnesia<br>Placebo consists in calcined magnesia, capsule of 1 gram each, taken every 8 hours before meals for 90 days. | Other: Calcined magnesia<br>* White, odor, color and flavorless thin powder.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brachial - ankle pulse wave velocity | Change in the pulse wave velocity | 90 days | 
| Flow mediated dilation | Change in the capacity of dilation of the brachial artery | 90 days | 
| Brachial - ankle index | Change in the systolic and diastolic pressures of the brachial and tibial arteries, the index is the result of dividing the last between the first | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systolic and diastolic blood pressure | Millimeters of mercury. mmHg | 4 visits: days 1, 30, 60 and 90. | 
| Blood glucose | Milligrams over deciliters. mg/dL | 4 visits: days 1, 30, 60 and 90. | 
| Glycated hemoglobin | Percentage | 4 visits: days 1, 30, 60 and 90. | 
| Lipid profile | Total cholesterol, triglycerides, high density lipoprotein, very high density lipoprotein, low density lipoprotein. All of them expressed in milligrams over deciliters. mg/dL | 4 visits: days 1, 30, 60 and 90. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cassia cinnamon, Endothelial function, Pulse wave velocity, Brachial - ankle index