Clinical trial NCT01543074: Dietary Histone Deacetylase Inhibitors (HDAC)
Official title: Dietary Histone Deacetylase (HDAC) Inhibitors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Histone Deacetylase (HDAC) Activity
Keywords: HDAC
histone acetylation
broccoli sprout extract
garlic oil
PBMCs
Lead sponsor: Texas A&M University
Sponsor class: OTHER
First posted: 2012-03-02
Enrollment: 23
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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.

Eligibility 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

Primary outcomes:
measure: Cmax of Sulforaphane and Its Metabolites in Blood
timeFrame: 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.
measure: Tmax of Sulforaphane and Its Metabolites in Blood
timeFrame: 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.
Secondary outcomes:
measure: Histone Acetylation
timeFrame: 6 h
Other outcomes:
Locations:
city: Corvallis
country: United States
facility: Oregon State University
state: Oregon
Study officials:
affiliation: Texas A&M University
name: Roderick Dashwood, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.