Aged Garlic Extract Study

Study Overview
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Brief Summary
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The primary intention of the study is to examine the effect of aged garlic extract (AGE) on the absolute change in coronary artery calcium (CAC). The second intention is to examine the effect of AGE on inflammatory biomarkers and microcirculation. It is a double blind placebo controlled study. The participants will ingest AGE during a period of one year. The CAC will be controlled by computer tomography (CT) scan; the inflammatory biomarkers through blood sample test and the microcirculation through laser speckel imagining and laser doppler before and after the one year period of AGE ingestion.

Detailed Description
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Objectives: Effect on coronary artery atherosclerosis / the progression of atherosclerosis Effect on inflammatory and oxidation biomarkers Cholesterol lowering effect Effect on microcirculation Type of study: Randomized double blind controlled trial Number of patients: 80 patients Duration of the study: The patients will be studied for one year after they have entered the study. The total time of the study duration from the including date of the first patient to the analysis of the last patient entering the study estimated to be 2-3 years. An inclusion rate off 1 to 2 patients per week. Treatment: Dose: Treated with a placebo capsule or a capsule containing a total of AGE 2400 mg daily for 1 year (2 Kyolic capsule (600 mg) twice daily). Methods: Placebo-controlled double blind randomized trial to determine whether AGE can influence the rate of atherosclerosis plaque burden measured by coronary artery calcium, improve vascular function and microcirculation and favorably change biomarkers of oxidative stress. Randomization: The participants are assigned to AGE or placebo in a double-blinded manner, using numbered containers assigned to a computer-generated randomization chart by a nurse coordinator.

Official Title
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Aged Garlic Extract (Kyolic) Study at Lund University, Sweden

Conditions
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Coronary Artery Disease, Microcirculation, Biomarkers

Intervention / Treatment
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* Dietary Supplement: Aged Garlic Extract
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CAC score >10 Framingham risk score (10 % or above) Subjects are required to be on stable concomitant medications for at least 12 weeks prior to randomization Subjects with diabetic must have HbA1C < 8.0, and stable HbA1C level variation range within 0.5% for three months. Exclusion Criteria: Hypersensitivity to AGE therapy, Unstable medical, psychiatric, or substance abuse disorder that may interfere with continuation in the study, Weight ≥325 pounds, Bleeding disorder, History of myocardial infarction, Stroke Life-threatening arrhythmia within prior 6 months, Resting hypotension (systolic < 90 mmHg) or hypertension (resting blood pressure >170/110) Heart failure NYHA class III or IV, History of malignancy within the last 5 years (other than skin cancer) or evidence of active cancer which would require concomitant cancer chemotherapy Serum creatinine >1.4 mg/dl Triglycerides > 400 at baseline visit Diabetic subjects with HbA1C > 8 %, Drug or alcohol abuse Conditions interfering with accurate assessment of coronary calcification (metal clips, bypass patients, intracoronary stents) and drug absorption (partial ileal bypass or malabsorption syndrome). Current use of anticoagulants (except for antiplatelet agents) Chronic renal failure Liver failure Hematological or biochemical values at baseline visit outside the reference ranges considered as clinically significant.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double blind placebo controlled prospective study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Aged Garlic Extract<br>The participants will ingest 600 mg of Aged Garlic Extract in two capsules two times a day i.e. 1200 mg/day during a period of one year. | Dietary Supplement: Aged Garlic Extract<br> <br> * Other names: Kyolic;|
| Placebo Comparator: Placebo<br>The participants will ingest 600 mg of placebo in two capsules two times a day i.e. 1200 mg/day during a period of one year. | Dietary Supplement: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in coronary artery calcium (CAC) score | CAC is to be defined as a plaque of at least three contiguous pixels (area 1.02 mm 2) with a density of > 130 Hounsfield units. The lesion score are to be calculated by multiplying the lesion area by a density factor derived from the maximal Hounsfield unit within this area, as described by Agatston S, Janowitz WR, Hildner FJ et al. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 1990; 15: 827-832. CAC score is measured at baseline and after one year follow-up and the difference is calculated. | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The changes in inflammatory biomarkers. | Changes in C-reactive protein (CRP mg/L) | One Year | 
| The changes in Interleukin-6 (IL-6) | Changes in IL-6 (ng/L) | One Year | 
| The changes in inflammatory biomarkers. | Changes in Homocystein (µmol/L) | One Year | 
| The changes in the microcirculation measured by Laser Doppler velocimetry | Laser Doppler Flowmetry (LDF) is a non-invasive method to estimate the blood perfusion in the microcirculation. The advantage of the technique is that LDF provide a continuous or near continuous record of the microvascular blood flow. No current laser Doppler instrument can present absolute perfusion values (e.g. ml/min/100 gram tissue). Measurements are expressed as perfusion units (PU) which are arbitrary. The changes in PU will be measured. | One Year | 
| Changes in Low Density Lipoprotein | Changes of Low Density Lipoprotein (LDL) mmol/L | One Year | 
| Changes in Triglycerides | Changes of Triglycerides mmol/L. | One Year | 
| Changes in Cholesterol | Changes of cholesterol mmol/L. | One Year | 
| Changes in High Density Lipoprotein | Changes of High Density Lipoprotein(HDL) mmol/L, | One Year | 
| Changes in lipid profile | Apolipoprotein B (mmol/L)/Apolipoprotein A1 (mmol/L) | One Year | 
| Changes in blood sugar | Changes in fastening blood glucose measured as mmol/L | One Year | 
| Changes in Blood pressure | Changes of blood pressure Systolic and Diastolic presented as mmHg. | One Year | 
| Changes in BMI | Changes in BMI measured as weight (kg) and height (m) and will be combined to report BMI in kg/m^2 | One Year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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garlic