AGE: Aged Garlic Extract Study

• Sponsor: Lund University Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT03860350
• Collaborator: (none)
• Enrollment: 100
• Location: 1
• Arms: 2
• Actual Duration (Months): 30
• Patients Per Site Per Month: 3.3

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease; Microcirculation; Biomarkers	Dietary Supplement: Aged Garlic Extract; Dietary Supplement: Placebo	N/A

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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Double blind placebo controlled prospective studyDouble blind placebo controlled prospective study
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: Aged Garlic Extract (Kyolic) Study at Lund University, Sweden
• Actual Study Start Date: Dec 1, 2016
• Actual Primary Completion Date: Jun 1, 2019
• Actual Study Completion Date: Jun 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Aged Garlic Extract 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; Other Names: Kyolic
Placebo Comparator: Placebo 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

Outcome Measures

Primary Outcome Measures

1. Change in coronary artery calcium (CAC) score [One year]

   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

1. The changes in inflammatory biomarkers. [One Year]

   Changes in C-reactive protein (CRP mg/L)

2. The changes in Interleukin-6 (IL-6) [One Year]

   Changes in IL-6 (ng/L)

3. The changes in inflammatory biomarkers. [One Year]

   Changes in Homocystein (µmol/L)

4. The changes in the microcirculation measured by Laser Doppler velocimetry [One Year]

   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.

5. Changes in Low Density Lipoprotein [One Year]

   Changes of Low Density Lipoprotein (LDL) mmol/L

6. Changes in Triglycerides [One Year]

   Changes of Triglycerides mmol/L.

7. Changes in Cholesterol [One Year]

   Changes of cholesterol mmol/L.

8. Changes in High Density Lipoprotein [One Year]

   Changes of High Density Lipoprotein(HDL) mmol/L,

9. Changes in lipid profile [One Year]

   Apolipoprotein B (mmol/L)/Apolipoprotein A1 (mmol/L)

10. Changes in blood sugar [One Year]

    Changes in fastening blood glucose measured as mmol/L

11. Changes in Blood pressure [One Year]

    Changes of blood pressure Systolic and Diastolic presented as mmHg.

12. Changes in BMI [One Year]

    Changes in BMI measured as weight (kg) and height (m) and will be combined to report BMI in kg/m^2

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Skane University Hospital	Lund		Sweden	22241

Sponsors and Collaborators

• Lund University Hospital

Investigators

• Principal Investigator: Sandra Lindstedt, MD, PhD, Skane University Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.
• Lindstedt S, Malmsjö 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.
• Lindstedt S, Malmsjö 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.
• Lindstedt S, Malmsjö 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.
• Lindstedt S, Malmsjö 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.

• Responsible Party: Sandra Lindstedt Ingemansson, Senior Consultant and Associate Professor, Lund University Hospital
• ClinicalTrials.gov Identifier: NCT03860350
• Other Study ID Numbers: DNR2016/745
• First Posted: Mar 1, 2019
• Last Update Posted: Jun 11, 2019
• Last Verified: Jun 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• 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
• Keywords provided by Sandra Lindstedt Ingemansson, Senior Consultant and Associate Professor, Lund University Hospital: garlic
• Additional relevant MeSH terms: Coronary Artery Disease

Study Results

No Results Posted as of Jun 11, 2019