Clinical trial NCT01715480: Effect of Broccoli Sprouts Homogenate on SS RBC
Official title: Physiological Effect of Sulforaphane Obtained From Broccoli Sprouts Homogenates (BSH) on the HbF and Anti-oxidative Capacity of Human Sickle Red Blood Cells (SS RBC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sickle Red Blood Cell
Fetal Hemoglobin
Oxidative Stress
Keywords: broccoli sprout
sickle cell
NRF2
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Doris Duke Charitable Foundation
First posted: 2012-10-29
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: The overall purpose of this study is to obtain a better understanding of the biological response of red blood cells to sulforaphane contained in fresh broccoli sprouts that have been put through a blending process. This study will use commercially available fresh broccoli sprouts certified by Brassica Protection Products LLC (BroccoSprouts®). This product can also be purchased at some local grocery stores in the produce section. It is believed that NRF2, a transcription factor encoded by the NFE2L2 gene, plays a role in the regulation of defense against oxidative stress. The detrimental accelerated breakdown of sickle cell disease (SCD) red blood cells (SS RBC) is partially due to reduced anti-oxidative capacity. Previous analysis of SS RBC microRNAs revealed that a reduced level of NRF2, the master regulator of anti-oxidative stress capacity, contributes to reduced resistance to oxidative stress and increased hemolysis; NRF2 also induces fetal hemoglobin (HbF), which is known to prevent SS RBC sickling.

First, erythroid progenitors from normal and SCD subjects will be tested ex-vivo to find out how sulforaphane, a natural NRF2 activator, affects the oxidative stress capacity, HbF expression, and microRNA expression of red cells.

Second, a pilot clinical trial will be conducted to determine the safety and physiological effects of 3 weeks of daily consumption of broccoli sprout homogenate in a cohort of Hb SS/SB0 thalassemia adult SCD patients. During this study, subjects RBCs will be assayed for changes in anti-oxidative stress capacity and microRNA composition in mature SCD red blood cells.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of Hemoglobin (Hb) SS or Hb Sβ0 thalassemia by electrophoresis
* Age ≥18 years
* Hematocrit (Hct) ≥ 20% and Hb \> 6.0 g/dL
* Capacity to understand and sign informed consent and can adhere to the daily regimen of BSH

Exclusion Criteria:

* RBC transfusion or change in hydroxyurea dose during the 3 months prior to study entry
* Ongoing pregnancy
* Diabetes
* Renal insufficiency (BUN \>21 mg/dL and/or Creatinine \>1.4 mg/dL)
* History of allergy to sulfonamides

Primary outcomes:
measure: In vitro response of HbAA and HbSS erythroid cells to NRF2 activation by sulforaphane.
timeFrame: 3 months
measure: Safety, physiological effects and cellular effects of daily consumption of broccoli sprout homogenate in a cohort of Hb SS/SB0 thalassemia adult SCD patients
timeFrame: 1-2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Jen-Tsan A Chi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Marilyn J Telen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sangokoya C, Telen MJ, Chi JT. microRNA miR-144 modulates oxidative stress tolerance and associates with anemia severity in sickle cell disease. Blood. 2010 Nov 18;116(20):4338-48. doi: 10.1182/blood-2009-04-214817. Epub 2010 Aug 13.
citation: Doss JF, Jonassaint JC, Garrett ME, Ashley-Koch AE, Telen MJ, Chi JT. Phase 1 Study of a Sulforaphane-Containing Broccoli Sprout Homogenate for Sickle Cell Disease. PLoS One. 2016 Apr 12;11(4):e0152895. doi: 10.1371/journal.pone.0152895. eCollection 2016.