Sickle Cell Disease
Conditions
Brief summary
The objective of this proposal is to test the feasibility of red blood cell (RBC) rejuvenation to chronic transfusion in sickle cell disease (SCD) and the potential benefit of RBC rejuvenation in this population to determine if a larger clinical trial powered to definitively characterize the benefits of rejuvenation is warranted. This is a small pilot study is to see if restoring important energy molecules (ATP and 2,3,DPG) in stored red blood cells before they are transfused, with a rejuvenating solution (Rejuvesol), offers any advantages to individuals over standard blood transfusion. Subjects will receive either rejuvenated (R) or standard (S) RBCs with each transfusion for 6 transfusions (over approximately a 6-month period) in a pre-defined order to maximize detection of any signal.
Detailed description
Blood transfusion is part of the standard care for individuals that have sickle cell disease. Often these transfusions become needed quite frequently. The purpose of the red blood cells in the blood is to deliver oxygen to the organs and tissues of the body. People with sickle cell disease have abnormal red blood cells. Stored blood undergoes some changes that may make it less effective in achieving this goal. The purpose of this study is to see if restoring important energy molecules (ATP and 2,3,DPG) in stored red blood cells before they are transfused, with a rejuvenating solution (Rejuvesol), offers any advantages to individuals over standard blood transfusion. This is a Food and Drug Administration (FDA) approved process that is described by the American Association of Blood Banks for prolonging blood storage but not used for everyday transfusions. The investigators want to use this process to improve blood transfused to individuals who need frequent transfusions. Potential advantages include better delivery of oxygen by the transfused red blood cells and easier release of oxygen to the tissues. In addition the study will assess how using the rejuvenated blood affects the interval between transfusions. This means possibly that transfusions may not be needed as often. Although Rejuvesol has been previously approved by the FDA, it is not routinely used to prepare standard blood transfusions to individuals who have sickle cell disease. Use of Rejuvesol in this study is considered investigational.
Interventions
DRUGRejuvesol
PROCEDUREBlood transfusion
Only transfusions necessary for the treatment of the sickle cell disease will be given for the purpose of the study.
Sponsors
Duke University
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Stable, compliant, chronically transfused sickle cell disease (SCD) patients * Currently maintained crisis-free with repeated RBC therapy for at least 3 consecutive sessions * ≥18 years old * Have Hb SS disease * Have the capacity to give informed consent
Exclusion criteria
* Baseline need for washed RBCs * Pre-treatment SaO2 \< 92%.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Percent Hemoglobin (HbA) Decrement Per Day | 6 months | The %HbA decrement is the current pre-treatment HbA - previous post treatment HbA in %. The average %HbA decrement per day was calculated using matched pairs. |
Secondary
| Measure | Time frame |
|---|---|
| Actual HbA Decrement (g/dl) With Indexing to Calculated Circulating Blood Volume | 6 months |
| Actual HbA Decrement (g/dl) Without Indexing to Calculated Circulating Blood Volume | 6 months |
| Change in RBC Microparticles (MP) Counts | 6 months |
| Change in RBC/RBC-MP-mediated Thrombin Generation | 6 months |
| Change in p50 Pre- and Post-transfusion | 6 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Each participant in this 4 subject pilot study acted as their own control. Red cell exchanges (RCEs) occurred approximately every month and, over a 6 month period, the sequence of exchanges for each patient was: SRRRSS, where S=standard and R=rejuvenated RCEs. | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| First Rejuvenated RCE | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment United States | 4 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 0 / 4 | 0 / 4 |
| serious Total, serious adverse events | 0 / 4 | 0 / 4 |
Outcome results
Primary
Average Percent Hemoglobin (HbA) Decrement Per Day
The %HbA decrement is the current pre-treatment HbA - previous post treatment HbA in %. The average %HbA decrement per day was calculated using matched pairs.
Time frame: 6 months
Population: Each participant acted as their own control with a sequence of rejuvenated and standard exchanges over 6 months. One subject ended further study participation after only 1 rejuvenated RBC exchange; limited data available.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Transfusion With Rejuvenated Red Blood Cells (RBCs) | Average Percent Hemoglobin (HbA) Decrement Per Day | 0.629 %HbA per day |
| Transfusion With Standard Red Blood Cells | Average Percent Hemoglobin (HbA) Decrement Per Day | 0.659 %HbA per day |
p-value: 0.95ANOVA
Secondary
Actual HbA Decrement (g/dl) With Indexing to Calculated Circulating Blood Volume
Time frame: 6 months
Population: Data not collected.
Secondary
Actual HbA Decrement (g/dl) Without Indexing to Calculated Circulating Blood Volume
Time frame: 6 months
Population: Data not collected.
Secondary
Change in p50 Pre- and Post-transfusion
Time frame: 6 months
Population: Data not collected.
Secondary
Change in RBC Microparticles (MP) Counts
Time frame: 6 months
Population: Data not collected.
Secondary
Change in RBC/RBC-MP-mediated Thrombin Generation
Time frame: 6 months
Population: Data not collected.