Effect of Broccoli Sprouts Homogenate on SS RBC

NCT01715480 | Completed DMC

• 1 other identifier: Pro00033630
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

Sickle Red Blood Cell; Fetal Hemoglobin; Oxidative Stress

Keywords

broccoli sprout; sickle cell; NRF2

Outcome Measures

Primary Outcomes (2)

• In vitro response of HbAA and HbSS erythroid cells to NRF2 activation by sulforaphane.

  Erythroid progenitor cells from 3 volunteers with Hb AA and 3 subjects with Hb SS disease will be exposed to sulforaphane and then their expression levels of genes regulated by Nrf2 will be measured.

  3 months

• Safety, physiological effects and cellular effects of daily consumption of broccoli sprout homogenate in a cohort of Hb SS/SB0 thalassemia adult SCD patients

  Adult subjects with Hb SS/SB0 thalassemia will be recruited to participate in this part of the study. Subjects will be asked to consume broccoli sprout that have been blended into a milkshake-like substance daily for three consecutive weeks. Safety measures will include recording of vital signs and adverse signs and symptoms. Assessment of physiological effects will include measurement of blood chemistries, counts, LDH, and hemoglobin F level. Measurements of cellular effects will include changes in microRNA gene profiling, gene expression profiling, and quantitation of anti-oxidant capacity.

  1-2 years

Study Arms (1)

Broccoli sprout homogenate ingestion

EXPERIMENTAL

Subjects will ingest broccoli sprout homogenate in the form of a shake.

Dietary Supplement: Broccosprouts® (Brassica Protection Products LLC) homogenate

Interventions

Broccosprouts® (Brassica Protection Products LLC) homogenate DIETARY_SUPPLEMENT

In the in-vitro part of the study, sulphoraphane will be added into the culture media used to grow and differentiate the erythroid cells from blood samples obtained from three Hb AA volunteers and three Hb SS subjects. The subjects will have a single clinic visit for the blood donation. In the second part of the study, enrolled subjects will be asked to consume homogenates of broccoli sprouts by mouth daily for three weeks. They will have a maximum of five clinic visits for medical assessments and lab draws during this time. They will then have a final clinic visit after a washout period of six weeks.

Also known as: Broccoli sprout

Broccoli sprout homogenate ingestion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Duke University: lead
• Doris Duke Charitable Foundation: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (2)

• 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.

  PMID: 20709907 BACKGROUND

• 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.

  PMID: 27071063 DERIVED

MeSH Terms

Conditions

beta-Thalassemia

Condition Hierarchy (Ancestors)

Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Jen-Tsan A Chi, MD, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

• Marilyn J Telen, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2012
• First Posted: October 29, 2012
• Study Start: March 1, 2012
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: May 28, 2015

Record last verified: 2015-02

Locations

US (1)