Dietary Histone Deacetylase Inhibitors (HDAC)

• ClinicalTrials.gov Identifier: NCT01543074
• Recruitment Status: Terminated
• First Posted: March 2, 2012
• Results First Posted: September 10, 2015
• Last Update Posted: April 30, 2019
• Sponsor: Texas A&M University
• Information provided by (Responsible Party): Roderick Dashwood, Texas A&M University

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	Not Applicable

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 (Clinical Trial)
• 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: February 2013
• Actual Primary Completion Date: December 2013
• Actual Study Completion Date: December 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 Name: Placebo for Broccoli Sprout Extract; Dietary Supplement: Garlic Oil Placebo; 1 pill = 0 mg garlic oil/day; Other Name: 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 Name: Placebo for Broccoli Sprout Extract; Dietary Supplement: Garlic oil; 1 pill = 30 mg garlic oil/day; Other Name: 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 Name: Broccoli Sprout Extract; Dietary Supplement: Garlic Oil Placebo; 1 pill = 0 mg garlic oil/day; Other Name: 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 Name: Schiff Super Garlic; Drug: BSE; 2 pills = 200 micromoles of Sulforaphane/day; Other Name: Broccoli Sprout Extract

Outcome Measures

Primary Outcome Measures :

1. Cmax of Sulforaphane and Its Metabolites in Blood [ 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. ]
   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 [ 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. ]
   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 [ Time Frame: 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

• Ages Eligible for Study: 20 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

United States, Oregon

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

More Information

Publications of Results:

Rajendran P, Dashwood WM, Li L, Kang Y, Kim E, Johnson G, Fischer KA, Lohr CV, Williams DE, Ho E, Yamamoto M, Lieberman DA, Dashwood RH. Nrf2 status affects tumor growth, HDAC3 gene promoter associations, and the response to sulforaphane in the colon. Clin Epigenetics. 2015 Sep 18;7(1):102. doi: 10.1186/s13148-015-0132-y. eCollection 2015.

• 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: March 2, 2012
• Results First Posted: September 10, 2015
• Last Update Posted: April 30, 2019
• Last Verified: April 2019

Keywords provided by Roderick Dashwood, Texas A&M University:

HDAC; histone acetylation; broccoli sprout extract; garlic oil; PBMCs

Additional relevant MeSH terms:

Allyl sulfide; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs; Anticarcinogenic Agents; Antineoplastic Agents; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors