Firefighter Aged Garlic Extract Investigation With CoQ10 as a Treatment for Heart Disease (FAITH)

• Sponsor: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00860847
• Collaborator: (none)
• Enrollment: 65
• Location: 1
• Arms: 2
• Duration (Months): 16
• Patients Per Site Per Month: 4.1

Study Details

Study Description

Brief Summary

1. Statement of Problem

According to the National Fire Protection Association (NFPA), 43.7% of all firefighters that died on the job experienced sudden cardiac death. The job also affords an incredible amount of stress. Cholesterol therapy has been well demonstrated to reduce coronary plaque progression. However is certainly not the only factor in evaluating for progression of coronary artery disease (CAD), and other factors must play a role. Garlic therapy has been shown to retard atherosclerosis independently.

1. Hypothesis and Specific Aims The hypothesis of this proposal is: In comparison to the placebo group, Aged Garlic Extract (AGE) therapy + Coenzyme Q10 (CoQ10) will be effective in slowing progression of coronary artery calcification (CAC) in firefighters with established atherosclerosis, independent of baseline blood pressure, statin use or other cardiovascular risk factors.

Specific Aims:

1. Compare the effects of cholesterol lowering effects in a firefighter population of patients under the influence of Aged Garlic Extract + CoQ10 or placebo.

2. Compare whether degree of change in atherosclerotic coronary artery plaque burden will change at a different rate under the influence of Aged Garlic Extract + CoQ10 compared to placebo treatment.

3. Compare whether Aged Garlic Extract + CoQ10 therapy induces changes in baseline values including biological and biochemical parameters, such as LDL cholesterol, homocysteine, C-reactive protein (CRP), and endothelial function.

Condition or Disease	Intervention/Treatment	Phase
Coronary Atherosclerosis; Coronary Artery Calcification; Coronary Stenosis	Dietary Supplement: Aged garlic extract and Coenzyme Q10	Phase 3

Detailed Description

Inclusion Criteria

• Calcium scan with Agatston score >20

• Age 35-84 years

• Subjects must provide written informed consent after the scope and nature of the investigation has been explained to them

• Subjects should be stable on their concomitant medications for at least 12 weeks prior to randomization

• Subjects who agree to refrain from supplemental garlic or significant dietary garlic

Exclusion Criteria

• A contraindication to Aged Garlic Extract therapy including: known hypersensitivity to drug.

• Any unstable medical, psychiatric or substance abuse disorder that in the opinion of the investigator or principal investigator is likely to affect the subject's ability to complete the study or precludes the subject's participation in the study

• Weight in excess of 325 pounds

• Bleeding disorder

• History of myocardial infarction, stroke or life-threatening arrhythmia within the prior six months

• Resting hypotension (a resting systolic blood pressure of <90 mm Hg) or hypertension (a resting blood pressure > 170 mm Hg or a resting diastolic blood pressure of >110 mm Hg)

• NYHA Class III or IV heart failure

• 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 visit 1

• Diabetic subjects with HbA1c > 12%

• Drug or alcohol abuse, or current intake of more than 14 standard drinks per week

• Concurrent enrollment in another placebo-controlled trial

• Presence of metal clips (i.e. bypass patients) or intracoronary stenting that preclude accurate measure of coronary calcification

• Partial ileal bypass or known gastrointestinal disease limiting drug absorption

• Current intake of garlic supplement or other prohibited drug (Appendix B)

• Current tobacco use

• Current use of anticoagulants (except for antiplatelet agents)

• Chronic renal failure

• Hematological or biochemical values at screening outside the reference ranges considered as clinically significant in the opinion of the investigator or PI

Outcome Measures Primary - Rate of change in total coronary calcium scores by CT The Agatston score was calculated by multiplying the lesion area (mm^2) by a density factor. The density was measured in Hounsfield units, and score of 1 for 130-199 HU, 2 for 200-299 HU, 3 for 300-399 HU, and 4 for 400 HU and greater.

Secondary Change in blood values and endothelial function over 6 and 12 months:

1. Plasma lipids: total plasma cholesterol and triglycerides, LDL-Cholesterol, HDL-Cholesterol, and VLDL-Cholesterol determined by the precipitation method;

2. Endothelial markers and inflammation: C-reactive protein and Homocysteine, as well as GSH

Study Design

• Study Type: Interventional
• Actual Enrollment: 65 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Firefighter Aged Garlic Extract Investigation With CoQ10 as a Treatment for Heart Disease (FAITH)
• Study Start Date: May 1, 2009
• Actual Primary Completion Date: Aug 1, 2010
• Actual Study Completion Date: Sep 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Aged Garlic Extract and Coenzyme Q10 AGE (1200 mg) and CoQ10 (120 mg) This is a combination of aged garlic extract and co-enzyme Q10	Dietary Supplement: Aged garlic extract and Coenzyme Q10; AGE (1200 mg) and CoQ10 (120 mg); Other Names: Kyolic formula 110
No Intervention: Placebo placebo pills will be given

Outcome Measures

Primary Outcome Measures

1. Rate of Change in Total Coronary Calcium Scores by Computed Tomography [1 year]

   progression of coronary artery calcium deposits as determined by computed tomography as measured by the Agatston score: The Agatston score was calculated by multiplying the lesion area (mm^2) by a density factor. The density was measured in Hounsfield units, and score of 1 for 130-199 HU, 2 for 200-299 HU, 3 for 300-399 HU, and 4 for 400 HU and greater The endpoint is the mean change (end of study value - baseline value) in each group.

Secondary Outcome Measures

1. 1.Plasma Lipids: Total Plasma Cholesterol and Triglycerides, LDL-Cholesterol, HDL-Cholesterol, and VLDL-Cholesterol Determined by the Precipitation Method; 2. Endothelial Markers and Inflammation: C-reactive Protein and Homocysteine, as Well as GSH [1 year]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 35 Years to 84 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Calcium scan with Agatston score >20

• Age 35-84 years

• Subjects must provide written informed consent after the scope and nature of the investigation has been explained to them

• Subjects should be stable on their concomitant medications for at least 12 weeks prior to randomization

• Subjects who agree to refrain from supplemental garlic or significant dietary garlic

Exclusion Criteria:

• A contraindication to Aged Garlic Extract therapy including: known hypersensitivity to drug.

• Any unstable medical, psychiatric or substance abuse disorder that in the opinion of the investigator or principal investigator is likely to affect the subject's ability to complete the study or precludes the subject's participation in the study

• Weight in excess of 325 pounds

• Bleeding disorder

• History of myocardial infarction, stroke or life-threatening arrhythmia within the prior six months

• Resting hypotension (a resting systolic blood pressure of <90 mm Hg) or hypertension (a resting blood pressure > 170 mm Hg or a resting diastolic blood pressure of >110 mm Hg)

• NYHA Class III or IV heart failure

• 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 visit 1

• Diabetic subjects with HbA1c > 12%

• Drug or alcohol abuse, or current intake of more than 14 standard drinks per week

• Concurrent enrollment in another placebo-controlled trial

• Presence of metal clips (i.e. bypass patients) or intracoronary stenting that preclude accurate measure of coronary calcification

• Partial ileal bypass or known gastrointestinal disease limiting drug absorption

• Current intake of garlic supplement or other prohibited drug (Appendix B)

• Current tobacco use

• Current use of anticoagulants (except for antiplatelet agents)

• Chronic renal failure

• Hematological or biochemical values at screening outside the reference ranges considered as clinically significant in the opinion of the investigator or PI

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Los Angeles Biomedical Research Institute	Torrance	California	United States	90005

Sponsors and Collaborators

• Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Investigators

• Principal Investigator: Matthew J Budoff, MD, University of California, Los Angeles

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Contact Drs Budoff or Laidlaw for further information

Publications

• Ahmadi N, Hajsadeghi F, Gul K, Vane J, Usman N, Flores F, Nasir K, Hecht H, Naghavi M, Budoff M. Relations between digital thermal monitoring of vascular function, the Framingham risk score, and coronary artery calcium score. J Cardiovasc Comput Tomogr. 2008 Nov;2(6):382-8. doi: 10.1016/j.jcct.2008.09.001. Epub 2008 Sep 26.
• BEUTLER E, DURON O, KELLY BM. Improved method for the determination of blood glutathione. J Lab Clin Med. 1963 May;61:882-8.
• Budoff MJ, Takasu J, Flores FR, Niihara Y, Lu B, Lau BH, Rosen RT, Amagase H. Inhibiting progression of coronary calcification using Aged Garlic Extract in patients receiving statin therapy: a preliminary study. Prev Med. 2004 Nov;39(5):985-91.
• Lau BH, Li L, Yoon P. Thymic peptide protects vascular endothelial cells from hydrogen peroxide-induced oxidant injury. Life Sci. 1993;52(22):1787-96.
• Libby P, Schoenbeck U, Mach F, Selwyn AP, Ganz P. Current concepts in cardiovascular pathology: the role of LDL cholesterol in plaque rupture and stabilization. Am J Med. 1998 Feb 23;104(2A):14S-18S. Review.
• Mao S, Bakhsheshi H, Lu B, Liu SC, Oudiz RJ, Budoff MJ. Effect of electrocardiogram triggering on reproducibility of coronary artery calcium scoring. Radiology. 2001 Sep;220(3):707-11.
• Raggi P, Callister TQ, Shaw LJ. Progression of coronary artery calcium and risk of first myocardial infarction in patients receiving cholesterol-lowering therapy. Arterioscler Thromb Vasc Biol. 2004 Jul;24(7):1272-7. Epub 2004 Apr 1.
• Steiner M, Lin RS. Changes in platelet function and susceptibility of lipoproteins to oxidation associated with administration of aged garlic extract. J Cardiovasc Pharmacol. 1998 Jun;31(6):904-8.
• Weissberg PL, Bennett MR. Atherosclerosis--an inflammatory disease. N Engl J Med. 1999 Jun 17;340(24):1928-9.

• Responsible Party: Matthew J. Budoff, Professor of Medicine, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
• ClinicalTrials.gov Identifier: NCT00860847
• Other Study ID Numbers: Wakunaga of America Co., Ltd.
• First Posted: Mar 12, 2009
• Last Update Posted: Mar 12, 2015
• Last Verified: Feb 1, 2015

• Keywords provided by Matthew J. Budoff, Professor of Medicine, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center: Progression of Atherosclerosis; Aged garlic extract; Biomarkers of inflammation; Coronary Plaque Volume and coronary Stenosis; Vascular function
• Additional relevant MeSH terms: Heart Diseases; Atherosclerosis; Coronary Stenosis; Coronary Artery Disease; Myocardial Ischemia; Ubiquinone; Coenzyme Q10

Study Results

Participant Flow

Recruitment Details	65 patients were recruited
Pre-assignment Detail	completed

Arm/Group Title	Aged Garlic Extract and Coenzyme Q10	Placebo
Arm/Group Description	Patients randomized to oral AGE (1200 mg) and CoQ10 (120 mg)	Patients randomized to placebo
Period Title: Overall Study
STARTED	32	33
COMPLETED	28	28
NOT COMPLETED	4	5

Baseline Characteristics

Arm/Group Title	Aged Garlic Extract and Coenzyme Q10	Placebo	Total
Arm/Group Description	Patients randomized to oral AGE (1200 mg) and CoQ10 (120 mg)	Patients randomized to placebo	Total of all reporting groups
Overall Participants	32	33	65
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	32 100%	33 100%	65 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55 (6)	55 (6)	55 (6)
Sex: Female, Male (Count of Participants)
Female	15 46.9%	16 48.5%	31 47.7%
Male	17 53.1%	17 51.5%	34 52.3%
Region of Enrollment (participants) [Number]
United States	32 100%	33 100%	65 100%

Outcome Measures

1. Primary Outcome

Title	Rate of Change in Total Coronary Calcium Scores by Computed Tomography
Description	progression of coronary artery calcium deposits as determined by computed tomography as measured by the Agatston score: The Agatston score was calculated by multiplying the lesion area (mm^2) by a density factor. The density was measured in Hounsfield units, and score of 1 for 130-199 HU, 2 for 200-299 HU, 3 for 300-399 HU, and 4 for 400 HU and greater The endpoint is the mean change (end of study value - baseline value) in each group.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

all participants were analyzed

Arm/Group Title	Aged Garlic Extract and Coenzyme Q10	Placebo
Arm/Group Description	Patients randomized to oral AGE (1200 mg) and CoQ10 (120 mg)	Patients randomized to placebo
Measure Participants	32	33
Mean (Standard Deviation) [Agatston score change]	32 (6)	58 (8)

2. Secondary Outcome

Title	1.Plasma Lipids: Total Plasma Cholesterol and Triglycerides, LDL-Cholesterol, HDL-Cholesterol, and VLDL-Cholesterol Determined by the Precipitation Method; 2. Endothelial Markers and Inflammation: C-reactive Protein and Homocysteine, as Well as GSH
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	1 year
Arm/Group Title	Aged Garlic Extract and Coenzyme Q10		Placebo
Arm/Group Description	Patients randomized to oral AGE (1200 mg) and CoQ10 (120 mg)		Patients randomized to placebo
All Cause Mortality
	Aged Garlic Extract and Coenzyme Q10		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Aged Garlic Extract and Coenzyme Q10		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/32 (0%)		0/33 (0%)
Other (Not Including Serious) Adverse Events
	Aged Garlic Extract and Coenzyme Q10		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/32 (0%)		0/33 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.