Clinical trial NCT03860350: Aged Garlic Extract Study
Official title: Aged Garlic Extract (Kyolic) Study at Lund University, Sweden
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Coronary Artery Disease
Microcirculation
Biomarkers
Keywords: garlic
Lead sponsor: Lund University Hospital
Sponsor class: OTHER
First posted: 2019-03-01
Enrollment: 100
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double blind placebo controlled prospective study
Primary purpose: OTHER

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.

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.

Primary outcomes:
measure: Change in coronary artery calcium (CAC) score
timeFrame: One year
Secondary outcomes:
measure: The changes in inflammatory biomarkers.
timeFrame: One Year
measure: The changes in Interleukin-6 (IL-6)
timeFrame: One Year
measure: The changes in inflammatory biomarkers.
timeFrame: One Year
measure: The changes in the microcirculation measured by Laser Doppler velocimetry
timeFrame: One Year
measure: Changes in Low Density Lipoprotein
timeFrame: One Year
measure: Changes in Triglycerides
timeFrame: One Year
measure: Changes in Cholesterol
timeFrame: One Year
measure: Changes in High Density Lipoprotein
timeFrame: One Year
measure: Changes in lipid profile
timeFrame: One Year
measure: Changes in blood sugar
timeFrame: One Year
measure: Changes in Blood pressure
timeFrame: One Year
measure: Changes in BMI
timeFrame: One Year
Other outcomes:
Locations:
city: Lund
country: Sweden
facility: Skane University Hospital
Study officials:
affiliation: Skane University Hospital
name: Sandra Lindstedt, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.
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.
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.