Sickle Cell DiseasePhase 1NCT02659644
A Study of Oral L-citrulline in Sickle Cell Disease
A Phase 1 study testing Oral L-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 that can result in blocking of the small blood vessels from sickle shaped red blood cells. This causes pain, the main feature of sickle cell disease. Read more about this study
- Who is it for?
- Ages 10 to 25 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Oral L-citrulline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2015to 31 Dec 2017
- Phase
- Phase 1
- 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 10 to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Sickle cell disease genotypes (HbSS, HbS/β-thalassemia
- HbS/β+thalassemia, HbSC)
- Patients with sickle cell disease aged 10 to 25 years old
- Patients ages 10 through 17 years of age, whose parents have signed permission, and who provide signed patient assent themselves
- Patients 18 through 25 years of age who provide signed consent.
Who cannot join
- 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
Show all 11Show fewer
- 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: 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 assent (ages 10 to 17 years) or consent (ages 18 through 25 years) will be excluded
- History of diabetes due to risk of electrolyte imbalance
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 I Dose-Ranging Study of Oral L-citrulline in Steady-State Sickle Cell
Sickle cell disease is a genetic red blood cell disorder that can result in blocking of the small blood vessels from sickle shaped red blood cells. This causes pain, the main feature of sickle cell disease. Also, low amounts of nitric oxide can occur in sickle cell disease, a substance important for widening the blood vessel wall and therefore preventing blockage of the small blood vessels.
Citrulline is a drug that is known to increase nitric oxide. This is a phase I study of citrulline given by mouth to evaluate the safety, tolerability and appropriate dosing of this medication for individuals with sickle cell disease.
- Conditions
- Sickle Cell Disease
- Being tested
- Oral L-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.
Oral L-citrullineDrug
There will be a total of 16 patients divided into 4 equal cohorts. The first 4 cohorts will be started on a 7 day oral regimen of twice daily L-citrulline. They will return to clinic on day #7 to evaluate nitric oxide metabolite levels and pharmacokinetic (PK) profile of citrulline. After PK analysis, the next cohort of patients will be given a higher or lower dose based on their weight and also based safety and tolerability. Of note, a PK analysis will be performed for each 4 patient cohort prior to starting citrulline for the subsequent cohort. Assessment for adverse events will be done at specified times throughout the study duration via both phone and clinic encounters.
| Study group | Role | What they receive |
|---|---|---|
| Oral citrulline | Experimental | Not described Receives: Drug: Oral L-citrulline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak plasma citrulline concentration (Cmax)
Measured: 7 days
Rate of citrulline appearance (Rapp)
Measured: 7 days
Constant of citrulline removal (krem)
Measured: 7 days
Volume of distribution
Measured: 7 days
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Measured: 7 days
Secondary outcomes (1)
Level of nitric oxide
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2016 (estimated)
- Study startDec 2015
- Primary completion31 Dec 2017 (estimated)
- Study completion31 Dec 2017
Why it stopped: Principal Investigator moved to another institution
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)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
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 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
- NCT02659644
- Sponsor's protocol ID
- 2015-0191
- Status last verified
- Jun 2018
- First submitted
- 29 Dec 2015
- Last updated
- 21 Jun 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Schwedhelm E, Maas R, Freese R, Jung D, Lukacs Z, Jambrecina A, Spickler W, Schulze F, Boger RH. Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. Br J Clin Pharmacol. 2008 Jan;65(1):51-9. doi: 10.1111/j.1365-2125.2007.02990.x. Epub 2007 Jul 27.
PubMed 17662090Moinard C, Nicolis I, Neveux N, Darquy S, Benazeth S, Cynober L. Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic study. Br J Nutr. 2008 Apr;99(4):855-62. doi: 10.1017/S0007114507841110. Epub 2007 Oct 22.
PubMed 17953788
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Dose-Ranging Study of Oral L-citrulline in Steady-State Sickle Cell
- ClinicalTrials.gov ID
- NCT02659644
- Acronym / sponsor ID
- 2015-0191
- Conditions
- Sickle Cell Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Principal Investigator moved to another institution
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Mississippi Medical CenterUniversity, hospital or other
- Study start
- Dec 2015
- Primary completion
- 31 Dec 2017 (estimated)
- Study completion
- 31 Dec 2017 (actual)
- First posted
- 20 Jan 2016 (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.
Sickle cell disease is a genetic red blood cell disorder that can result in blocking of the small blood vessels from sickle shaped red blood cells. This causes pain, the main feature of sickle cell disease. Also, low amounts of nitric oxide can occur in sickle cell disease, a substance important for widening the blood vessel wall and therefore preventing blockage of the small blood vessels.
Citrulline is a drug that is known to increase nitric oxide. This is a phase I study of citrulline given by mouth to evaluate the safety, tolerability and appropriate dosing of this medication for individuals with sickle cell disease.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Oral citrulline | Experimental | Drug: Oral L-citrulline |
Who may qualify
- Ages
- 10 to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Sickle cell disease genotypes (HbSS, HbS/β-thalassemia
- HbS/β+thalassemia, HbSC)
- Patients with sickle cell disease aged 10 to 25 years old
- Patients ages 10 through 17 years of age, whose parents have signed permission, and who provide signed patient assent themselves
- Patients 18 through 25 years of age who provide signed consent.
Key exclusion criteria (11 listed)
- 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
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 |
|---|---|---|
| Oral L-citrullineThere will be a total of 16 patients divided into 4 equal cohorts. The first 4 cohorts will be started on a 7 day oral regimen of twice daily L-citrulline. They will return to clinic on day #7 to evaluate nitric oxide metabolite levels and pharmacokinetic (PK) profile of citrulline. After PK analysis, the next cohort of patients will be given a higher or lower dose based on their weight and also based safety and tolerability. Of note, a PK analysis will be performed for each 4 patient cohort prior to starting citrulline for the subsequent cohort. Assessment for adverse events will be done at specified times throughout the study duration via both phone and clinic encounters. | Drug | Oral citrulline |
Primary outcome
Peak plasma citrulline concentration (Cmax)
Time frame: 7 days
Rate of citrulline appearance (Rapp)
Time frame: 7 days
Constant of citrulline removal (krem)
Time frame: 7 days
Volume of distribution
Time frame: 7 days
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: 7 days
1 secondary outcome
Level of nitric oxide
Time frame: 7 days
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 21 Jun 2018.
- Background: PubMed 17662090Schwedhelm E, Maas R, Freese R, Jung D, Lukacs Z, Jambrecina A, Spickler W, Schulze F, Boger RH. Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. Br J Clin Pharmacol. 2008 Jan;65(1):51-9. doi: 10.1111/j.1365-2125.2007.02990.x. Epub 2007 Jul 27.
- Background: PubMed 17953788Moinard C, Nicolis I, Neveux N, Darquy S, Benazeth S, Cynober L. Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic study. Br J Nutr. 2008 Apr;99(4):855-62. doi: 10.1017/S0007114507841110. Epub 2007 Oct 22.
- 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 Oral L-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 5 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 21 Jun 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 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?
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?
Peak plasma citrulline concentration (Cmax) (time frame: 7 days). The study lists 5 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 NCT02659644, which also lists 2 linked publications.
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 21 Jun 2018.