Dietary Histone Deacetylase Inhibitors (HDAC)

• Sponsor: Texas A&M University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01543074
• Collaborator: (none)
• Enrollment: 23
• Location: 1
• Arms: 4
• Duration (Months): 10
• Patients Per Site Per Month: 2.3

Study Details

Study Description

Brief Summary

This pilot, three-week study will help scientists understand more about how the foods people eat can modify histone deacetylases, enzymes the body produces naturally. Broccoli sprout extract (BSE) and garlic oil are thought to modify these enzymes. The purpose of this study is to see if taking broccoli sprout extract alone, garlic oil alone, or broccoli sprout extract and garlic oil together, can decrease the action of histone deacetylase (HDAC) and turn on genes in white blood cells. There will be 80 people in this study.

Condition or Disease	Intervention/Treatment	Phase
Histone Deacetylase (HDAC) Activity	Dietary Supplement: BSE placebo; Dietary Supplement: Garlic oil; Drug: BSE; Dietary Supplement: Garlic Oil Placebo	N/A

Detailed Description

Study participants attend a pre-study meeting either individually or with several other potential volunteers according to their preference. The study is described in detail and participants are given the opportunity to ask questions. If participants agree to participate, they will sign the consent form. Height and weight will be measured privately.

Food diary forms will be distributed and taught how to use. A 4ml (1 tsp) blood sample will be drawn for a pre-study blood chemistry, CBC and thyroid tests. Samples for all clinical labs done during the study will be sent to Good Samaritan Hospital, a CLIA-certified laboratory, on a fee-for-service basis.

The study MD will evaluate the lab results. If the tests are abnormal as determined by the study MD, the participant will be excluded from the study and advised to see their doctor for evaluation.

Subjects will observe dietary restrictions starting one week before Day 1 of the study and continuing through Day 14 (total of 3 weeks). Dietary restrictions are listed on the last page of the diet recall forms.

Women with negative urine pregnancy test on the morning of Day 1 will be enrolled in the study. About 20 ml fasting blood will be drawn on the morning of Day 1. Breakfast will be provided and 3 capsules given to swallow. (One capsule will be garlic oil or garlic oil placebo, the other two will be BSE or BSE placebo.) No eating or drinking (except water) until the next blood draws at 1,3 6 hours after breakfast.

Participants will come to the study site for the next seven days to consume the standard breakfast and study capsules, or we may send the breakfast and study capsules home with participants for the weekend. Blood will be sampled immediately before breakfast on day 7 and again at 1, 3, 6, 24 and 48 hours later. We will provide a standardized lunch to all participants on Days 1 and 7. Additional blood draws will occur at the end of week 2 (i.e. on day 14 of the study). The study will end after 2 weeks.

Participants will fill out a dietary recall form three random times during the study on two week days and one weekend day.

Urine will be collected on the following schedule: Day 1, 0-3 hours, 3-6 hours, 6-12 hours,12-24 hours, 24-48 hours; Day 7, 0-3 hours, 3-6 hours, 6-12 hours, 12-24 hours, 24-48 hours. Total urine from each interval will be collected and pooled in separate containers. We will provide the proper containers for urine collection. Urine may be stored at room temperature.

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: Dietary Histone Deacetylase (HDAC) Inhibitors
• Study Start Date: Feb 1, 2013
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: BSE placebo & garlic oil placebo Two BSE placebo capsules and one garlic oil placebo capsule per day for seven days	Dietary Supplement: BSE placebo; 2 pills = 0 micromoles of Sulforaphane/day; Other Names: Placebo for Broccoli Sprout Extract ; Dietary Supplement: Garlic Oil Placebo; 1 pill = 0 mg garlic oil/day; Other Names: Placebo for Schiff Super Garlic
Active Comparator: garlic oil plus BSE placebo one garlic oil capsule plus 2 BSE placebo capsules per day for seven days	Dietary Supplement: BSE placebo; 2 pills = 0 micromoles of Sulforaphane/day; Other Names: Placebo for Broccoli Sprout Extract ; Dietary Supplement: Garlic oil; 1 pill = 30 mg garlic oil/day; Other Names: Schiff Super Garlic
Active Comparator: BSE plus garlic oil placebo two BSE capsules plus one garlic oil placebo capsule per day for seven days	Drug: BSE; 2 pills = 200 micromoles of Sulforaphane/day; Other Names: Broccoli Sprout Extract ; Dietary Supplement: Garlic Oil Placebo; 1 pill = 0 mg garlic oil/day; Other Names: Placebo for Schiff Super Garlic
Active Comparator: BSE & Garlic Oil two BSE and one garlic oil capsule per day for seven days	Dietary Supplement: Garlic oil; 1 pill = 30 mg garlic oil/day; Other Names: Schiff Super Garlic ; Drug: BSE; 2 pills = 200 micromoles of Sulforaphane/day; Other Names: Broccoli Sprout Extract

Outcome Measures

Primary Outcome Measures

1. Cmax of Sulforaphane and Its Metabolites in Blood [Before breakfast (0 hours) and 1, 3 and 6 hours after breakfast & pills on Days 1 & 7, and before breakfast on Days 8, 9 and 14.]

   The levels of "Sulforaphane and its metabolites (combined)" in blood was measured using Liquid Chromatrography-Mass Spectrometry (LC-MS) methods. Cmax (mean +/- SD) values are shown in the "Outcome Measure Data Table".

2. Tmax of Sulforaphane and Its Metabolites in Blood [Before breakfast (0 hours) and 1, 3 and 6 hours after breakfast & pills on Days 1 & 7, and before breakfast on Days 8, 9 and 14.]

   The levels of "Sulforaphane and its metabolites (combined)" in blood was measured using Liquid Chromatrography-Mass Spectrometry (LC-MS) methods. The time to achieve highest plasma concentration (Tmax) is shown in the "Outcome Measure Data Table".

Secondary Outcome Measures

1. Histone Acetylation [6 h]

   Histone acetylation was measured by immunoblotting the levels of acetylated histone H4K12 in the circulating peripheral blood mononuclear cells (PBMCs) of subjects who consumed either placebo, garlic oil, BSE, or BSE+garlic oil. The fold increase in acetylated histone H4K12 in the different groups is shown in the "Outcome Measure Data Table".

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion criteria:

• age: 20 and older

• body mass index 19-30 kg/sq m

• willingness to maintain normal exercise and activity patterns

• willingness to avoid cruciferous vegetables and garlic and related foods (onion etc.) 1 week before and 2 weeks during the trial for a total of 3 weeks

Exclusion criteria:

• tobacco use within the past three months

• engaging in aerobic activity more than 6 hours per week

• being vegetarian or having other restrictive dietary requirements

• consuming >3 alcoholic beverages/day or >10 per week

• having history of diabetes or uremia or other known metabolic disease

• participating in another dietary study within the past three months

• for women, being pregnant or breastfeeding

• gastrointestinal diseases that could increase gut permeability, including Crohn's disease, ulcerative colitis, gastritis

• taking dietary supplements other than those given in the study

• abnormal liver function, CBC, or thyroid values

• individuals taking any drug or medication, prescription or over the counter, including Isoniazid, Saquinavir, Warfarin, Cyclosporine, Acetaminophen, Oxazepam, medications used for HIV/ AIDS, blood clotting, birth control pills, fish oil and medications metabolized by CYPs (CYP1A2, CYP2E1 and CYP3A4) during the dosing period of 1 week and 48 h prior to and after dosing. Exceptions may be made by the study MD and the PI if in their opinion a medication will not interfere with the scientific validity of the study. The study MD will evaluate a medication on a case-by-case basis to determine that efficacy and safety are not adversely affected.

• Individuals who are known to have problems with blood clotting or increased bleeding, including hemophiliacs or anyone recently undergoing or recovering from a surgical procedure.

• soy or garlic allergy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Oregon State University	Corvallis	Oregon	United States	97331

Sponsors and Collaborators

• Texas A&M University

Investigators

• Principal Investigator: Roderick Dashwood, PhD, Texas A&M University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Roderick Dashwood, Director Center for Epigenetics & Disease Prevention, Texas A&M University
• ClinicalTrials.gov Identifier: NCT01543074
• Other Study ID Numbers: CA122959
• First Posted: Mar 2, 2012
• Last Update Posted: Apr 30, 2019
• Last Verified: Apr 1, 2019

• Keywords provided by Roderick Dashwood, Director Center for Epigenetics & Disease Prevention, Texas A&M University: HDAC; histone acetylation; broccoli sprout extract; garlic oil; PBMCs
• Additional relevant MeSH terms: Allyl sulfide

Study Results

Participant Flow

Recruitment Details	34 Subjects consented for the study at the Linus Pauling Institute clinic, Corvallis, Oregon during the period February, 2013 to November, 2013. However, only 23 who qualified the criteria in the pre-screen blood tests were selected for the study.

Arm/Group Title	BSE Placebo & Garlic Oil Placebo	Garlic Oil Plus BSE Placebo	BSE Plus Garlic Oil Placebo	BSE & Garlic Oil
Arm/Group Description	Two BSE placebo capsules and one garlic oil placebo capsule per day for seven days BSE placebo & garlic oil placebo: see arm description BSE & Garlic Oil: see arm description	one garlic oil capsule plus 2 BSE placebo capsules per day for seven days BSE placebo & garlic oil placebo: see arm description BSE plus garlic oil placebo: see arm description	two BSE capsules plus one garlic oil placebo capsule per day for seven days garlic oil plus BSE placebo: see arm description BSE & Garlic Oil: see arm description	two BSE and one garlic oil capsule per day for seven days garlic oil plus BSE placebo: see arm description BSE plus garlic oil placebo: see arm description
Period Title: Overall Study
STARTED	5	7	5	6
COMPLETED	5	7	5	6
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	BSE Placebo & Garlic Oil Placebo	Garlic Oil Plus BSE Placebo	BSE Plus Garlic Oil Placebo	BSE & Garlic Oil	Total
Arm/Group Description	Two BSE placebo capsules and one garlic oil placebo capsule per day for seven days BSE placebo & garlic oil placebo: see arm description BSE & Garlic Oil: see arm description	one garlic oil capsule plus 2 BSE placebo capsules per day for seven days BSE placebo & garlic oil placebo: see arm description BSE plus garlic oil placebo: see arm description	two BSE capsules plus one garlic oil placebo capsule per day for seven days garlic oil plus BSE placebo: see arm description BSE & Garlic Oil: see arm description	two BSE and one garlic oil capsule per day for seven days garlic oil plus BSE placebo: see arm description BSE plus garlic oil placebo: see arm description	Total of all reporting groups
Overall Participants	5	7	5	6	23
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	27.8 (14.1)	29.9 (10.1)	30.8 (17.2)	33.7 (18.1)	30 (14)
Sex: Female, Male (Count of Participants)
Female	4 80%	3 42.9%	4 80%	1 16.7%	12 52.2%
Male	1 20%	4 57.1%	1 20%	5 83.3%	11 47.8%
Region of Enrollment (participants) [Number]
United States	5 100%	7 100%	5 100%	6 100%	23 100%

Outcome Measures

1. Primary Outcome

Title	Cmax of Sulforaphane and Its Metabolites in Blood
Description	The levels of "Sulforaphane and its metabolites (combined)" in blood was measured using Liquid Chromatrography-Mass Spectrometry (LC-MS) methods. Cmax (mean +/- SD) values are shown in the "Outcome Measure Data Table".
Time Frame	Before breakfast (0 hours) and 1, 3 and 6 hours after breakfast & pills on Days 1 & 7, and before breakfast on Days 8, 9 and 14.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BSE Placebo & Garlic Oil Placebo	Garlic Oil Plus BSE Placebo	BSE Plus Garlic Oil Placebo	BSE & Garlic Oil
Arm/Group Description	Two BSE placebo capsules and one garlic oil placebo capsule per day for seven days BSE placebo & garlic oil placebo: see arm description BSE & Garlic Oil: see arm description	one garlic oil capsule plus 2 BSE placebo capsules per day for seven days BSE placebo & garlic oil placebo: see arm description BSE plus garlic oil placebo: see arm description	two BSE capsules plus one garlic oil placebo capsule per day for seven days garlic oil plus BSE placebo: see arm description BSE & Garlic Oil: see arm description	two BSE and one garlic oil capsule per day for seven days garlic oil plus BSE placebo: see arm description BSE plus garlic oil placebo: see arm description
Measure Participants	5	7	5	6
Mean (Standard Deviation) [micromoles/L]	NA (NA)	NA (NA)	0.92 (0.15)	1.26 (0.17)

2. Primary Outcome

Title	Tmax of Sulforaphane and Its Metabolites in Blood
Description	The levels of "Sulforaphane and its metabolites (combined)" in blood was measured using Liquid Chromatrography-Mass Spectrometry (LC-MS) methods. The time to achieve highest plasma concentration (Tmax) is shown in the "Outcome Measure Data Table".
Time Frame	Before breakfast (0 hours) and 1, 3 and 6 hours after breakfast & pills on Days 1 & 7, and before breakfast on Days 8, 9 and 14.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BSE Placebo & Garlic Oil Placebo	Garlic Oil Plus BSE Placebo	BSE Plus Garlic Oil Placebo	BSE & Garlic Oil
Arm/Group Description	Two BSE placebo capsules and one garlic oil placebo capsule per day for seven days BSE placebo: 2 pills = 0 micromoles of Sulforaphane/day Garlic Oil Placebo: 1 pill = 0 mg garlic oil/day	one garlic oil capsule plus 2 BSE placebo capsules per day for seven days BSE placebo: 2 pills = 0 micromoles of Sulforaphane/day Garlic oil: 1 pill = 30 mg garlic oil/day	two BSE capsules plus one garlic oil placebo capsule per day for seven days BSE: 2 pills = 200 micromoles of Sulforaphane/day Garlic Oil Placebo: 1 pill = 0 mg garlic oil/day	two BSE and one garlic oil capsule per day for seven days Garlic oil: 1 pill = 30 mg garlic oil/day BSE: 2 pills = 200 micromoles of Sulforaphane/day
Measure Participants	5	7	5	6
Mean (Standard Deviation) [hours]	NA (NA)	NA (NA)	3 (0)	3 (0)

3. Secondary Outcome

Title	Histone Acetylation
Description	Histone acetylation was measured by immunoblotting the levels of acetylated histone H4K12 in the circulating peripheral blood mononuclear cells (PBMCs) of subjects who consumed either placebo, garlic oil, BSE, or BSE+garlic oil. The fold increase in acetylated histone H4K12 in the different groups is shown in the "Outcome Measure Data Table".
Time Frame	6 h

Outcome Measure Data

Analysis Population Description

The data were obtained by analyzing 'representative' patient samples (n=3 per group) using immunoblotting.

Arm/Group Title	BSE Placebo & Garlic Oil Placebo	Garlic Oil Plus BSE Placebo	BSE Plus Garlic Oil Placebo	BSE & Garlic Oil
Arm/Group Description	Two BSE placebo capsules and one garlic oil placebo capsule per day for seven days BSE placebo: 2 pills = 0 micromoles of Sulforaphane/day Garlic Oil Placebo: 1 pill = 0 mg garlic oil/day	one garlic oil capsule plus 2 BSE placebo capsules per day for seven days BSE placebo: 2 pills = 0 micromoles of Sulforaphane/day Garlic oil: 1 pill = 30 mg garlic oil/day	two BSE capsules plus one garlic oil placebo capsule per day for seven days BSE: 2 pills = 200 micromoles of Sulforaphane/day Garlic Oil Placebo: 1 pill = 0 mg garlic oil/day	two BSE and one garlic oil capsule per day for seven days Garlic oil: 1 pill = 30 mg garlic oil/day BSE: 2 pills = 200 micromoles of Sulforaphane/day
Measure Participants	3	3	3	3
Mean (Standard Deviation) [Fold change]	0.83 (0.15)	1.03 (0.15)	1.05 (0.21)	1.20 (0.26)

Adverse Events

Arm/Group Title	BSE Placebo & Garlic Oil Placebo		Garlic Oil Plus BSE Placebo		BSE Plus Garlic Oil Placebo		BSE & Garlic Oil
Arm/Group Description	Two BSE placebo capsules and one garlic oil placebo capsule per day for seven days BSE placebo & garlic oil placebo: see arm description BSE & Garlic Oil: see arm description		one garlic oil capsule plus 2 BSE placebo capsules per day for seven days BSE placebo & garlic oil placebo: see arm description BSE plus garlic oil placebo: see arm description		two BSE capsules plus one garlic oil placebo capsule per day for seven days garlic oil plus BSE placebo: see arm description BSE & Garlic Oil: see arm description		two BSE and one garlic oil capsule per day for seven days garlic oil plus BSE placebo: see arm description BSE plus garlic oil placebo: see arm description
All Cause Mortality
	BSE Placebo & Garlic Oil Placebo		Garlic Oil Plus BSE Placebo		BSE Plus Garlic Oil Placebo		BSE & Garlic Oil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	BSE Placebo & Garlic Oil Placebo		Garlic Oil Plus BSE Placebo		BSE Plus Garlic Oil Placebo		BSE & Garlic Oil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/7 (0%)		0/5 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	BSE Placebo & Garlic Oil Placebo		Garlic Oil Plus BSE Placebo		BSE Plus Garlic Oil Placebo		BSE & Garlic Oil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		1/7 (14.3%)		3/5 (60%)		1/6 (16.7%)
Gastrointestinal disorders
Abdominal discomfort	0/5 (0%)	0	1/7 (14.3%)	1	3/5 (60%)	3	1/6 (16.7%)	1

Limitations/Caveats

Early termination (23/80) due to small numbers of subjects recruited.

More Information

Certain Agreements

All Principal Investigators ARE 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.