Sickle Cell DiseasePhase 1NCT02697240
A Phase 1 Study of Continuous Intravenous L-citrulline During Sickle Cell Pain Crisis or Acute Chest Syndrome
A Phase 1 study testing Intravenous citrulline in people with Sickle Cell Disease, run by University of Mississippi Medical Center at 1 site in United States.
Trial summary
Sickle cell disease is a genetic red blood cell disorder characterized by vaso-occlusion from sickling of red blood cells, that can lead to pain or organ complications such as acute chest syndrome. Read more about this study
- Who is it for?
- Ages 6 to 50 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Intravenous citrulline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2016to Apr 2017
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 6 to 50 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Sickle cell disease genotypes (HbSS, HbS/β0-thalassemia, HbS/β+-thalassemia, HbSC)
- Ages 6 to 50 years old
- Patients with sickle cell disease aged 6 to 50 years old Presence of sickle cell pain crisis defined by the presence of pain requiring hospitalization and parental opioid therapy
- Presence of acute chest syndrome defined by the presence of a new CXR infiltrate and any one of the following respiratory symptoms of fever, shortness of breath, wheezing, chest pain, cough or new onset hypoxia.
Who cannot join
- 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, etc.
- Severe anemia (hemoglobin < 5g/dL)
- History of red blood cell transfusion within the last 30 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.
Show all 11Show fewer
- Subject has the following serum creatinine:
- Age 6 to 13 years > 0.9 mg/dL
- Age 14-17 years 1.0 mg/dL
- Age 18 years >1.5mg/dL
- Patients with an inability to give consent will be excluded
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Mississippi Medical Center
Jackson, Mississippi, 39216
About this study
Official title: A Phase 1 Dose Escalation Study of Continuous Intravenous L-citrulline During Sickle Cell Pain Crisis or Acute Chest Syndrome
Sickle cell disease is a genetic red blood cell disorder characterized by vaso-occlusion from sickling of red blood cells, that can lead to pain or organ complications such as acute chest syndrome. Sickle cell disease is associated with low amounts of nitric oxide, a compound important for dilating the blood vessel wall. Citrulline is a substance that is known to increase nitric oxide. The goal of this Phase I study are to find the highest safe dose of continuous IV citrulline that can be given to individuals with sickle cell disease experiencing a sickle cell pain crisis or acute chest syndrome without causing severe side effects.
- Conditions
- Sickle Cell Disease
- Being tested
- Intravenous citrulline
- Keywords
- sickle cell disease, citrulline
- 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.
Intravenous citrullineDrug
Intravenous citrulline at a bolus dose of 20 mg/kg over 5 minutes and then continuous at a rate of 7 mg/kg/hour for the next 23 hours for the first 7 participants, and depending on safety and pharmacokinetic profile, increase or decrease the continuous rate to 9 or 5 mg/kg/hour for the next 7 participants.
| Study group | Role | What they receive |
|---|---|---|
| Intravenous citrulline | Experimental | Intravenous citrulline at a bolus dose over 5 minutes and then a continuous rate for the next 23 hours. Receives: Drug: Intravenous citrulline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events
The number and severity of adverse event will be determined according to the NCI Common Terminology Criteria for Adverse Events (CTCAE)
Measured: 30 days
Plasma Citrulline Level
Measured: Plasma citrulline levels will be evaluated at the following time points: trough level, 10 minutes (peak level), 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours and 48 hours, to evaluate the pharmacokinetic profile
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2016 (estimated)
- Study startFeb 2016
- Primary completionApr 2017
- Study completionApr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Mississippi Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Suvankar Majumdar, University of Mississippi Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02697240
- Sponsor's protocol ID
- 2014-0230
- Status last verified
- Jun 2019
- First submitted
- 29 Feb 2016
- Last updated
- 25 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Barr FE, Tirona RG, Taylor MB, Rice G, Arnold J, Cunningham G, Smith HA, Campbell A, Canter JA, Christian KG, Drinkwater DC, Scholl F, Kavanaugh-McHugh A, Summar ML. Pharmacokinetics and safety of intravenously administered citrulline in children undergoing congenital heart surgery: potential therapy for postoperative pulmonary hypertension. J Thorac Cardiovasc Surg. 2007 Aug;134(2):319-26. doi: 10.1016/j.jtcvs.2007.02.043.
PubMed 17662768
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Dose Escalation Study of Continuous Intravenous L-citrulline During Sickle Cell Pain Crisis or Acute Chest Syndrome
- ClinicalTrials.gov ID
- NCT02697240
- Acronym / sponsor ID
- 2014-0230
- Conditions
- Sickle Cell Disease
- Keywords
- sickle cell disease, citrulline
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- University of Mississippi Medical CenterUniversity, hospital or other
- Study start
- Feb 2016
- Primary completion
- Apr 2017 (actual)
- Study completion
- Apr 2017 (actual)
- First posted
- 3 Mar 2016 (estimated)
- Results
- Posted 17 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Sickle cell disease is a genetic red blood cell disorder characterized by vaso-occlusion from sickling of red blood cells, that can lead to pain or organ complications such as acute chest syndrome. Sickle cell disease is associated with low amounts of nitric oxide, a compound important for dilating the blood vessel wall. Citrulline is a substance that is known to increase nitric oxide. The goal of this Phase I study are to find the highest safe dose of continuous IV citrulline that can be given to individuals with sickle cell disease experiencing a sickle cell pain crisis or acute chest syndrome without causing severe side effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intravenous citrulline | Experimental | Drug: Intravenous citrullineIntravenous citrulline at a bolus dose over 5 minutes and then a continuous rate for the next 23 hours. |
Who may qualify
- Ages
- 6 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Sickle cell disease genotypes (HbSS, HbS/β0-thalassemia, HbS/β+-thalassemia, HbSC)
- Ages 6 to 50 years old
- Patients with sickle cell disease aged 6 to 50 years old Presence of sickle cell pain crisis defined by the presence of pain requiring hospitalization and parental opioid therapy
- Presence of acute chest syndrome defined by the presence of a new CXR infiltrate and any one of the following respiratory symptoms of fever, shortness of breath, wheezing, chest pain, cough or new onset hypoxia.
Key exclusion criteria (11 listed)
- 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, etc.
- Severe anemia (hemoglobin < 5g/dL)
- History of red blood cell transfusion within the last 30 days
- Systemic steroid therapy within the last 48 hours
- Pregnant (as confirmed by a negative urine pregnancy test) or lactating female
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 |
|---|---|---|
| Intravenous citrullineIntravenous citrulline at a bolus dose of 20 mg/kg over 5 minutes and then continuous at a rate of 7 mg/kg/hour for the next 23 hours for the first 7 participants, and depending on safety and pharmacokinetic profile, increase or decrease the continuous rate to 9 or 5 mg/kg/hour for the next 7 participants. | Drug | Intravenous citrulline |
Primary outcome
Number of Participants With Adverse Events
Time frame: 30 days
The number and severity of adverse event will be determined according to the NCI Common Terminology Criteria for Adverse Events (CTCAE)
Plasma Citrulline Level
Time frame: Plasma citrulline levels will be evaluated at the following time points: trough level, 10 minutes (peak level), 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours and 48 hours, to evaluate the pharmacokinetic profile
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17662768Barr FE, Tirona RG, Taylor MB, Rice G, Arnold J, Cunningham G, Smith HA, Campbell A, Canter JA, Christian KG, Drinkwater DC, Scholl F, Kavanaugh-McHugh A, Summar ML. Pharmacokinetics and safety of intravenously administered citrulline in children undergoing congenital heart surgery: potential therapy for postoperative pulmonary hypertension. J Thorac Cardiovasc Surg. 2007 Aug;134(2):319-26. doi: 10.1016/j.jtcvs.2007.02.043.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Intravenous citrulline in people with Sickle Cell Disease, run by University of Mississippi Medical Center 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: finished, as of the sponsor's last update on 25 Jun 2019. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Adverse Events (time frame: 30 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02697240, which also lists 1 linked publication.
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 25 Jun 2019.