Back to resultsAged Garlic Extract Study (AGE)
Primary Purpose
Coronary Artery Disease, Microcirculation, Biomarkers
Status
Completed
Phase
Not Applicable
Locations
Sweden
Study Type
Interventional
Intervention
Aged Garlic Extract
Placebo
Sponsored by
About this trial
This is an interventional other trial for Coronary Artery Disease focused on measuring garlic
Eligibility Criteria
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.
Sites / Locations
- Skane University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Aged Garlic Extract
Placebo
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
The changes in inflammatory biomarkers.
Changes in C-reactive protein (CRP mg/L)
The changes in Interleukin-6 (IL-6)
Changes in IL-6 (ng/L)
The changes in inflammatory biomarkers.
Changes in Homocystein (µmol/L)
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.
Changes in Low Density Lipoprotein
Changes of Low Density Lipoprotein (LDL) mmol/L
Changes in Triglycerides
Changes of Triglycerides mmol/L.
Changes in Cholesterol
Changes of cholesterol mmol/L.
Changes in High Density Lipoprotein
Changes of High Density Lipoprotein(HDL) mmol/L,
Changes in lipid profile
Apolipoprotein B (mmol/L)/Apolipoprotein A1 (mmol/L)
Changes in blood sugar
Changes in fastening blood glucose measured as mmol/L
Changes in Blood pressure
Changes of blood pressure Systolic and Diastolic presented as mmHg.
Changes in BMI
Changes in BMI measured as weight (kg) and height (m) and will be combined to report BMI in kg/m^2
Full Information
NCT ID
NCT03860350
First Posted
February 26, 2019
Last Updated
June 8, 2019
Sponsor
Lund University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT03860350
Brief Title
Aged Garlic Extract Study
Acronym
AGE
Official Title
Aged Garlic Extract (Kyolic) Study at Lund University, Sweden
Study Type
Interventional
2. Study Status
Record Verification Date
June 2019
Overall Recruitment Status
Completed
Study Start Date
December 1, 2016 (Actual)
Primary Completion Date
June 1, 2019 (Actual)
Study Completion Date
June 1, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Lund University Hospital
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
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Disease, Microcirculation, Biomarkers
Keywords
garlic
7. Study Design
Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Double blind placebo controlled prospective study
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Aged Garlic Extract
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Dietary Supplement
Intervention Name(s)
Aged Garlic Extract
Other Intervention Name(s)
Kyolic
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Change in coronary artery calcium (CAC) score
Description
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.
Time Frame
One year
Secondary Outcome Measure Information:
Title
The changes in inflammatory biomarkers.
Description
Changes in C-reactive protein (CRP mg/L)
Time Frame
One Year
Title
The changes in Interleukin-6 (IL-6)
Description
Changes in IL-6 (ng/L)
Time Frame
One Year
Title
The changes in inflammatory biomarkers.
Description
Changes in Homocystein (µmol/L)
Time Frame
One Year
Title
The changes in the microcirculation measured by Laser Doppler velocimetry
Description
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.
Time Frame
One Year
Title
Changes in Low Density Lipoprotein
Description
Changes of Low Density Lipoprotein (LDL) mmol/L
Time Frame
One Year
Title
Changes in Triglycerides
Description
Changes of Triglycerides mmol/L.
Time Frame
One Year
Title
Changes in Cholesterol
Description
Changes of cholesterol mmol/L.
Time Frame
One Year
Title
Changes in High Density Lipoprotein
Description
Changes of High Density Lipoprotein(HDL) mmol/L,
Time Frame
One Year
Title
Changes in lipid profile
Description
Apolipoprotein B (mmol/L)/Apolipoprotein A1 (mmol/L)
Time Frame
One Year
Title
Changes in blood sugar
Description
Changes in fastening blood glucose measured as mmol/L
Time Frame
One Year
Title
Changes in Blood pressure
Description
Changes of blood pressure Systolic and Diastolic presented as mmHg.
Time Frame
One Year
Title
Changes in BMI
Description
Changes in BMI measured as weight (kg) and height (m) and will be combined to report BMI in kg/m^2
Time Frame
One Year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sandra Lindstedt, MD, PhD
Organizational Affiliation
Skane University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Skane University Hospital
City
Lund
ZIP/Postal Code
22241
Country
Sweden
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
2407762
Citation
Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol. 1990 Mar 15;15(4):827-32. doi: 10.1016/0735-1097(90)90282-t.
Results Reference
background
PubMed Identifier
22104565
Citation
Lindstedt S, Malmsjo M, Hansson J, Hlebowicz J, Ingemansson R. Microvascular blood flow changes in the small intestinal wall during conventional negative pressure wound therapy and negative pressure wound therapy using a protective disc over the intestines in laparostomy. Ann Surg. 2012 Jan;255(1):171-5. doi: 10.1097/SLA.0b013e31823c9ffa.
Results Reference
background
PubMed Identifier
23517436
Citation
Lindstedt S, Malmsjo M, Hlebowicz J, Ingemansson R. Comparative study of the microvascular blood flow in the intestinal wall, wound contraction and fluid evacuation during negative pressure wound therapy in laparostomy using the V.A.C. abdominal dressing and the ABThera open abdomen negative pressure therapy system. Int Wound J. 2015 Feb;12(1):83-8. doi: 10.1111/iwj.12056. Epub 2013 Mar 21.
Results Reference
background
PubMed Identifier
18062803
Citation
Lindstedt S, Malmsjo M, Ingemansson R. No hypoperfusion is produced in the epicardium during application of myocardial topical negative pressure in a porcine model. J Cardiothorac Surg. 2007 Dec 6;2:53. doi: 10.1186/1749-8090-2-53.
Results Reference
background
PubMed Identifier
17643636
Citation
Lindstedt S, Malmsjo M, Ingemansson R. Blood flow changes in normal and ischemic myocardium during topically applied negative pressure. Ann Thorac Surg. 2007 Aug;84(2):568-73. doi: 10.1016/j.athoracsur.2007.02.066.
Results Reference
background
PubMed Identifier
19573556
Citation
Budoff MJ, Ahmadi N, Gul KM, Liu ST, Flores FR, Tiano J, Takasu J, Miller E, Tsimikas S. Aged garlic extract supplemented with B vitamins, folic acid and L-arginine retards the progression of subclinical atherosclerosis: a randomized clinical trial. Prev Med. 2009 Aug-Sep;49(2-3):101-7. doi: 10.1016/j.ypmed.2009.06.018. Epub 2009 Jun 30.
Results Reference
background
PubMed Identifier
33868439
Citation
Wlosinska M, Nilsson AC, Hlebowicz J, Fakhro M, Malmsjo M, Lindstedt S. Aged Garlic Extract Reduces IL-6: A Double-Blind Placebo-Controlled Trial in Females with a Low Risk of Cardiovascular Disease. Evid Based Complement Alternat Med. 2021 Mar 31;2021:6636875. doi: 10.1155/2021/6636875. eCollection 2021.
Results Reference
derived
PubMed Identifier
32349742
Citation
Wlosinska M, Nilsson AC, Hlebowicz J, Hauggaard A, Kjellin M, Fakhro M, Lindstedt S. The effect of aged garlic extract on the atherosclerotic process - a randomized double-blind placebo-controlled trial. BMC Complement Med Ther. 2020 Apr 29;20(1):132. doi: 10.1186/s12906-020-02932-5.
Results Reference
derived
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Aged Garlic Extract Study
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