Sickle Cell AnemiaPhase 2NCT02162225
Study of Beet Juice for Patients With Sickle Cell Anemia
A Phase 2 study testing beet juice (Unbeetable) in people with Sickle Cell Anemia, run by Wake Forest University Health Sciences at 1 site in United States.
Trial summary
The investigators hypothesize that increasing plasma nitrite using dietary nitrate will improve platelet function and red cell deformability and decrease MCHC in patients with sickle cell disease. Read more about this study
- Who is it for?
- Ages 19 to 65 years
- Conditions the study is for
- Sickle Cell Anemia
- What is being tested?
- beet juice (Unbeetable)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2014to Apr 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- diagnosis of sickle cell anemia (Hb S/S or Hb S/beta thal0)
- no acute illness at the time of obtaining the study
- willingness to adhere to the study preparatory procedures including drinking the beet juice product daily
- willingness to give consent in order to participate
Who cannot join
- less than 19 years in age or older than 65
- smoke or chew tobacco
- currently take medications that affect stomach pH
- atrophic gastritis
- hypo-or hyperthyroidism
- Type I or II diabetes
Show all 11Show fewer
- history of gout, kidney stones or hypotension
- pregnant
- aversion to the study-related testing procedures
- allergy, sensitivity or aversion to the study beetroot juice beverage
- suffered an acute sickle cell episode (involving hospitalization or a visit to the emergency room) within the past six months
Trial locations and contacts
1 site in 1 country.
United States1 site
Wake Forest University School of Medicine
Winston-Salem, North Carolina, 27157
About this study
Official title: Phase 2 Study of Effects of Plasma Nitrite in Sickle Cell Anemia
The investigators hypothesize that increasing plasma nitrite using dietary nitrate will improve platelet function and red cell deformability and decrease MCHC in patients with sickle cell disease. The investigators will test this hypothesis through administration of daily intake of beetroot juice (Unbeetable - Performance Drink) to patients with sickle cell disease for 28 days. The investigators will evaluate the safety of daily beet root juice intake in patients with sickle cell disease. In addition, the investigators will measure MCHC, red cell deformability, and platelet function (activation and aggregation) in response to daily intake of beet root juice in this patient population.
Read the detailed description
Sickle cell disease is caused by dysfunction of a mutant form of hemoglobin which polymerizes under hypoxic conditions, sickling the red blood cell. Sickling makes the cells rigid which contributes to vascular occlusion and much morbidity and mortality. Cycles of sickling and unsickling leads to calcium (Ca) influx which activates the gardos channel which pumps out potassium from the cells. Loss of potassium leads to dehydration, poor deformability, and increased mean corpuscular hemoglobin concentration (MCHC) in red blood cells. Increased MCHC leads to increased polymerization. Thus, a significant therapeutic goal for sickle cell disease has been to decrease MCHC by blocking the Ca-influx induced dehydration.
Rifkind and coworkers have shown that the NO+ donor sodium nitrosoprusside (SNP) can block Ca-induced loss of deformability when normal red blood cells are exposed to Ca and a Ca ionophore. The investigators have preliminary data showing that both NO activity donors SNP and nitrite can partially relieve loss of deformability due to cycles of sickling and unsickling in red cells from patients with sickle cell disease.
Low nitric oxide (NO) bioavailabilty secondary to red cell hemolysis has been proposed to contribute to pathology in sickle cell disease. Low NO could lead to poor protection against Ca-induced potassium loss described above. Another consequence of low NO is likely to be increased platelet activation; sickle cell disease is pro-thrombotic disease. NO reduces platelet aggregation and activation. It has been shown that an acute dietary nitrate intervention can reduce platelet aggregation in healthy volunteers. Nitrate is converted to nitrite which is converted to NO in the body.6 Improved platelet function is likely due to increasing NO bioavailability through the nitrate intervention.
In this pilot study, the safety of Beet Juice intake in patients with sickle cell disease will be evaluated using a self-administered health survey. Physiological effects of the Beet Juice will also be examined and the investigators hypothesize that increasing plasma nitrite using dietary nitrate will improve platelet function and red cell deformability and decrease MCHC in patients with sickle cell disease. The investigators will test this hypothesis through administration of daily intake of Beet Juice to patients with sickle cell disease for 28 days. The investigators will measure MCHC, red cell deformability, and platelet function (activation and aggregation) in response to the intervention.
- Conditions
- Sickle Cell Anemia
- Being tested
- beet juice (Unbeetable)
- Keywords
- Erythrocyte Deformability, Platelet Activation, Platelet Aggregation, Nitrite, Sickle Cell Anemia, Diet Therapy
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
beet juice (Unbeetable)Drug
Volunteers will drink a single 8 ounce bottle of beet juice (Unbeetable) per day for 28 days.
On days 1,14, and 28, the juice will be drunk just prior to having blood drawn. Blood will also be drawn 1.5 hours after drinking the juice on days 1,14, and 28.
| Study group | Role | What they receive |
|---|---|---|
| Beet Juice | Experimental | Volunteers will drink a single 8 ounce bottle of beet juice (Unbeetable) per day for 28 days.
On days 1,14, and 28, the juice will be drunk just prior to having blood drawn. Blood will also be drawn 1.5 hours after drinking the juice on days 1,14, and 28. Receives: Drug: beet juice (Unbeetable) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Number of Participants with Adverse Events as a Measure of Safety and Tolerability as a function of time
Physical symptoms will be assessed either by telephone or in person
Measured: up to 58 Days
Secondary outcomes (2)
Changes in Red blood cell properties as a function of time
Blood will be drawn and used to measure red blood cell deformability and mean corpuscular hemoglobin concentration
Measured: Days 1, 14, 28
Changes in Platelet function as a function of time
Blood will be drawn and used to measure platelets activation and aggregation
Measured: Days 1, 14, 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2014 (estimated)
- Study startSep 2014
- Primary completionFeb 2019 (estimated)
- Study completionApr 2019 (estimated)
Why it stopped: Enrollment was very slow. Hope to reopen as multi-site study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell AnemiaStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Wake Forest University, National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Natalia Dixon, MD, Principal investigator, Wake Forest University Health SciencesDaniel B Kim-Shapiro, PhD, Study director, Wake Forest University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02162225
- Sponsor's protocol ID
- Wake-58091
- Other IDs
- R37HL058091
- Status last verified
- Jul 2018
- First submitted
- 9 Jun 2014
- Last updated
- 2 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Study of Effects of Plasma Nitrite in Sickle Cell Anemia
- ClinicalTrials.gov ID
- NCT02162225
- Acronym / sponsor ID
- Wake-58091
- Conditions
- Sickle Cell Anemia
- Keywords
- Erythrocyte Deformability, Platelet Activation, Platelet Aggregation, Nitrite, Sickle Cell Anemia, Diet Therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Enrollment was very slow. Hope to reopen as multi-site study
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- Wake Forest University, National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Sep 2014
- Primary completion
- Feb 2019 (estimated)
- Study completion
- Apr 2019 (estimated)
- First posted
- 12 Jun 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators hypothesize that increasing plasma nitrite using dietary nitrate will improve platelet function and red cell deformability and decrease MCHC in patients with sickle cell disease. The investigators will test this hypothesis through administration of daily intake of beetroot juice (Unbeetable - Performance Drink) to patients with sickle cell disease for 28 days. The investigators will evaluate the safety of daily beet root juice intake in patients with sickle cell disease. In addition, the investigators will measure MCHC, red cell deformability, and platelet function (activation and aggregation) in response to daily intake of beet root juice in this patient population.
Detailed description
Sickle cell disease is caused by dysfunction of a mutant form of hemoglobin which polymerizes under hypoxic conditions, sickling the red blood cell. Sickling makes the cells rigid which contributes to vascular occlusion and much morbidity and mortality. Cycles of sickling and unsickling leads to calcium (Ca) influx which activates the gardos channel which pumps out potassium from the cells. Loss of potassium leads to dehydration, poor deformability, and increased mean corpuscular hemoglobin concentration (MCHC) in red blood cells. Increased MCHC leads to increased polymerization. Thus, a significant therapeutic goal for sickle cell disease has been to decrease MCHC by blocking the Ca-influx induced dehydration.
Rifkind and coworkers have shown that the NO+ donor sodium nitrosoprusside (SNP) can block Ca-induced loss of deformability when normal red blood cells are exposed to Ca and a Ca ionophore. The investigators have preliminary data showing that both NO activity donors SNP and nitrite can partially relieve loss of deformability due to cycles of sickling and unsickling in red cells from patients with sickle cell disease.
Low nitric oxide (NO) bioavailabilty secondary to red cell hemolysis has been proposed to contribute to pathology in sickle cell disease. Low NO could lead to poor protection against Ca-induced potassium loss described above. Another consequence of low NO is likely to be increased platelet activation; sickle cell disease is pro-thrombotic disease. NO reduces platelet aggregation and activation. It has been shown that an acute dietary nitrate intervention can reduce platelet aggregation in healthy volunteers. Nitrate is converted to nitrite which is converted to NO in the body.6 Improved platelet function is likely due to increasing NO bioavailability through the nitrate intervention.
In this pilot study, the safety of Beet Juice intake in patients with sickle cell disease will be evaluated using a self-administered health survey. Physiological effects of the Beet Juice will also be examined and the investigators hypothesize that increasing plasma nitrite using dietary nitrate will improve platelet function and red cell deformability and decrease MCHC in patients with sickle cell disease. The investigators will test this hypothesis through administration of daily intake of Beet Juice to patients with sickle cell disease for 28 days. The investigators will measure MCHC, red cell deformability, and platelet function (activation and aggregation) in response to the intervention.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Beet Juice | Experimental | Drug: beet juice (Unbeetable)Volunteers will drink a single 8 ounce bottle of beet juice (Unbeetable) per day for 28 days. On days 1,14, and 28, the juice will be drunk just prior to having blood drawn. Blood will also be drawn 1.5 hours after drinking the juice on days 1,14, and 28. |
Who may qualify
- Ages
- 19 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- diagnosis of sickle cell anemia (Hb S/S or Hb S/beta thal0)
- no acute illness at the time of obtaining the study
- willingness to adhere to the study preparatory procedures including drinking the beet juice product daily
- willingness to give consent in order to participate
Key exclusion criteria (11 listed)
- less than 19 years in age or older than 65
- smoke or chew tobacco
- currently take medications that affect stomach pH
- atrophic gastritis
- hypo-or hyperthyroidism
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| beet juice (Unbeetable)Volunteers will drink a single 8 ounce bottle of beet juice (Unbeetable) per day for 28 days. On days 1,14, and 28, the juice will be drunk just prior to having blood drawn. Blood will also be drawn 1.5 hours after drinking the juice on days 1,14, and 28. | Drug | Beet Juice |
Primary outcome
Total Number of Participants with Adverse Events as a Measure of Safety and Tolerability as a function of time
Time frame: up to 58 Days
Physical symptoms will be assessed either by telephone or in person
2 secondary outcomes
Changes in Red blood cell properties as a function of time
Time frame: Days 1, 14, 28
Changes in Platelet function as a function of time
Time frame: Days 1, 14, 28
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Natalia Dixon, MD principal investigator
Wake Forest University Health Sciences
Daniel B Kim-Shapiro, PhD study director
Wake Forest University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing beet juice (Unbeetable) in people with Sickle Cell Anemia, run by Wake Forest University Health Sciences at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 2 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total Number of Participants with Adverse Events as a Measure of Safety and Tolerability as a function of time (time frame: up to 58 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2018; AzTrials last refreshed its copy on 7 Nov 2026.