Sickle Cell Disease
Conditions
Brief summary
The purpose of this study is to assess the maximum tolerated dose, safety and pharmacokinetics of an investigational drug, intravenous (IV) citrulline, in subjects in steady-state sickle cell disease.
Interventions
DRUGIntravenous (IV) citrulline
Sponsors
Suvankar Majumdar
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 25 Years
Healthy volunteers
No
Inclusion criteria
* Sickle cell disease genotypes (HbSS, HbS/β° thalassemia, HbS/β+thalassemia, HbSC)
Exclusion criteria
* Presence of any acute illness defined by fever \>100.4° F within the past 48 hours * Presence of sickle cell pain crisis defined by the presence of pain requiring oral or parental opioid therapy. * Presence of acute chest syndrome or presence of any other complication related to sickle cell disease requiring hospitalization such as splenic sequestration, hepatic sequestration, stroke, avascular necrosis of the hip/shoulder, acute priapism, and patients with diabetes etc. * Severe anemia (hemoglobin \< 5g/dL) * History of red blood cell transfusion within the last 14 days * Systemic steroid therapy within the last 48 hours * Pregnant (as confirmed by a negative urine pregnancy test) or lactating female * Alanine/aspartate transferase \>2x upper limit of normal laboratory range for age. * Elevated serum creatinine \>1.5mg/dL * Patients with an inability to give consent will be excluded * Medications that are known to be contra-indicated with use of L-citrulline (concurrent use of hydroxyurea will be allowed). * History of diabetes due to risk of electrolyte imbalance
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Grade 2 or Higher Adverse Event According to NCI Criteria | 12 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intravenous (IV) Citrulline Intravenous (IV) citrulline 20 mg/kg bolus with dose escalation of 10 mg/kg to target citrulline concentration of 100 µmol/L with a maximum dose of 60 mg/kg. | 4 |
| Total | 4 |
Baseline characteristics
| Characteristic | Intravenous (IV) Citrulline |
|---|---|
| Age, Continuous | 22.8 years |
| 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 | 2 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
Number of Participants With Grade 2 or Higher Adverse Event According to NCI Criteria
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IV Citrulline | Number of Participants With Grade 2 or Higher Adverse Event According to NCI Criteria | 0 participants |