Sickle Cell DiseasePhase 1NCT01685515
Study of Decitabine and Tetrahydrouridine (THU) in Patients With Sickle Cell Disease
A Phase 1 study testing Oral Decitabine and Tetrahydrouridine in people with Sickle Cell Disease, run by Yogen Saunthararajah at 1 site in United States.
Trial summary
The purposes of this study are to observe if oral tetrahydrouridine and decitabine can increase fetal hemoglobin levels and improve the symptoms of sickle cell disease, and to monitor how patient's bodies react to oral tetrahydrouridine and decitabine. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Oral Decitabine and Tetrahydrouridine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2012to Jun 2018
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 years or older.
- Written, informed consent provided by the subject before study entry.
- Confirmed Sickle Cell Disease (SCD) (SS, S-b0-thalassemia, S-b+-thalassemia or SC on hemoglobin electrophoresis).
- Symptomatic SCD while on 6 months of HU OR symptomatic SCD and intolerant of HU (unable or unwilling to take HU due to hematological or other toxicities). Symptomatic SCD is defined as having one of following:
- Fetal Hemoglobin (HbF) <5%, OR
- 3 or more pain episodes per year requiring parenteral narcotics, OR
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- 1 or more acute chest syndrome episodes, OR
- Hemoglobin <9 g/dL and absolute reticulocyte count <250,000/mm3.
- Subject is in his/her steady state and not amidst any acute complication due to SCD (i.e., hospitalization, acute pain, or acute chest syndrome in the past 14 days).
- Regular compliance with comprehensive care and previous therapy.
Who cannot join
- Inability to give informed consent.
- Experienced severe sepsis or septic shock within the previous 12 weeks.
- Last HU dose was ingested within the previous 4 weeks.
- Currently pregnant or breast-feeding.
- Alanine aminotransferase (ALT) greater than or equal to two times (2X) the upper limit of normal or albumin <2.0 mg/dL or direct (conjugated) bilirubin greater than or equal to 1.5 mg/dl.
- Serum creatinine >2.9 mg/dL and calculated creatinine clearance <30 mL/min.
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- Platelet count >800 x 109/L.
- Absolute neutrophil count <1.5 x 109/L.
- Female of active childbearing potential who is unwilling to use at least one of the two following forms of birth control:
- not having heterosexual sexual contact beginning at the screening visit and continuing until 4 weeks after the last dose of THU-decitabine OR (ii) intrauterine device (IUD).
- Sexually active male who is unwilling to use a condom when engaging in any sexual contact with a female with child-bearing potential, beginning at the screening visit and continuing until 4 weeks after taking the last dose of THU-decitabine. This requirement applies also to males who have had a successful vasectomy.
- Altered mental status or recurrent seizures requiring anti-seizure medications.
- Moribund or any concurrent disease (e.g., hepatic, renal, cardiac, metabolic) of such severity that death within 24 weeks is likely.
- Concurrent diagnosis of malignancy including myelodysplastic syndromes (MDS), leukemia, or an abnormal karyotype.
- Vitamin-B12, folate, or iron deficient (until corrected).
- New York Heart Association (NYHA) class III/IV status.
- Eastern Co-operative Oncology Group (ECOG) performance status greater than or equal to 3.
- Participant is on chronic transfusion therapy (e.g., for history of Transient Ischemic Attack (TIA) or stroke) and medically contraindicated to discontinue transfusions (unless multiple allo-antibodies prevent the patient from getting transfusions as scheduled).
- Known history of illicit drug or alcohol abuse within the past 12 months.
- Other experimental or investigational drug therapy in the past 28 days.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Illinois at Chicago
Chicago, Illinois, 60612
About this study
Official title: Phase 1 Study of Oral Decitabine and Tetrahydrouridine (THU) in Patients With High Risk Sickle Cell Disease
The purposes of this study are to observe if oral tetrahydrouridine and decitabine can increase fetal hemoglobin levels and improve the symptoms of sickle cell disease, and to monitor how patient's bodies react to oral tetrahydrouridine and decitabine.
Read the detailed description
The purposes of this study are to observe if oral tetrahydrouridine and decitabine can increase fetal hemoglobin levels and improve the symptoms of sickle cell disease, and to monitor how patient's bodies react to oral tetrahydrouridine and decitabine. The overall purpose is to develop disease modifying treatment for sickle cell disease that is less cytotoxic than the current standard of care, and which can directly and more efficiently reactivate fetal hemoglobin levels. The hypothesis is that patients treated with oral tetrahydrouridine and decitabine will have the same chance of severe non-hematologic toxicities as the placebo group. The primary end-point is ≥ grade 3 non-hematologic toxicity. The investigators' hypothesis is that patients in the treatment groups receiving oral THU-decitabine 2X/week over 8 weeks (n=15) will be equivalent to placebo group (n=10) with regards to the chance of ≥ grade 3 non-hematologic toxicity.
- Conditions
- Sickle Cell Disease
- Being tested
- Oral Decitabine and Tetrahydrouridine, Placebo
- 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 Decitabine and TetrahydrouridineDrug
Also called Dacogen, 5-aza-2'-deoxycytydine, THU
Oral Decitabine and Oral Tetrahydrouridine (THU) given 1-2 hours apart on 2 consecutive days over 8 weeks
PlaceboDrug
Also called Water
Plain water will be dispensed at a similar volume and in the same containers as study drug. The water placebo has a similar appearance and taste to the study drug, since the study drug is highly diluted in water.
| Study group | Role | What they receive |
|---|---|---|
| Oral Decitabine and Tetrahydrouridine | Experimental | Oral Decitabine and Tetrahydrouridine Receives: Drug: Oral Decitabine and Tetrahydrouridine |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Non-hematologic toxicity
Toxicities will be evaluated on a weekly basis and will be classified according to their grade and relationship to study treatment. Chi-square testing will be employed to examine the difference in number of patients with grade 3 or greater non-hematologic toxicity between treatment and placebo groups.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2012 (estimated)
- Study startAug 2012
- Primary completionJun 2018
- Study completionJun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yogen Saunthararajah
- Sponsor type
- University, hospital or other
- Collaborators
- University of Illinois Chicago
- Responsible party
- Sponsor-investigator, Yogen Saunthararajah, The Cleveland Clinic
- Investigators
- Yogen Saunthararajah, MD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01685515
- Sponsor's protocol ID
- CASE 10Z11
- Status last verified
- Sep 2018
- First submitted
- 6 Sep 2012
- Last updated
- 11 Sep 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Molokie R, Lavelle D, Gowhari M, Pacini M, Krauz L, Hassan J, Ibanez V, Ruiz MA, Ng KP, Woost P, Radivoyevitch T, Pacelli D, Fada S, Rump M, Hsieh M, Tisdale JF, Jacobberger J, Phelps M, Engel JD, Saraf S, Hsu LL, Gordeuk V, DeSimone J, Saunthararajah Y. Oral tetrahydrouridine and decitabine for non-cytotoxic epigenetic gene regulation in sickle cell disease: A randomized phase 1 study. PLoS Med. 2017 Sep 7;14(9):e1002382. doi: 10.1371/journal.pmed.1002382. eCollection 2017 Sep.
PubMed 28880867
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of Oral Decitabine and Tetrahydrouridine (THU) in Patients With High Risk Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT01685515
- Acronym / sponsor ID
- CASE 10Z11
- Conditions
- Sickle Cell Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Yogen SaunthararajahUniversity, hospital or other
- Collaborators
- University of Illinois Chicago
- Study start
- Aug 2012
- Primary completion
- Jun 2018 (actual)
- Study completion
- Jun 2018 (actual)
- First posted
- 14 Sep 2012 (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 purposes of this study are to observe if oral tetrahydrouridine and decitabine can increase fetal hemoglobin levels and improve the symptoms of sickle cell disease, and to monitor how patient's bodies react to oral tetrahydrouridine and decitabine.
Detailed description
The purposes of this study are to observe if oral tetrahydrouridine and decitabine can increase fetal hemoglobin levels and improve the symptoms of sickle cell disease, and to monitor how patient's bodies react to oral tetrahydrouridine and decitabine. The overall purpose is to develop disease modifying treatment for sickle cell disease that is less cytotoxic than the current standard of care, and which can directly and more efficiently reactivate fetal hemoglobin levels. The hypothesis is that patients treated with oral tetrahydrouridine and decitabine will have the same chance of severe non-hematologic toxicities as the placebo group. The primary end-point is ≥ grade 3 non-hematologic toxicity. The investigators' hypothesis is that patients in the treatment groups receiving oral THU-decitabine 2X/week over 8 weeks (n=15) will be equivalent to placebo group (n=10) with regards to the chance of ≥ grade 3 non-hematologic toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Oral Decitabine and Tetrahydrouridine | Experimental | Drug: Oral Decitabine and TetrahydrouridineOral Decitabine and Tetrahydrouridine |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age 18 years or older.
- Written, informed consent provided by the subject before study entry.
- Confirmed Sickle Cell Disease (SCD) (SS, S-b0-thalassemia, S-b+-thalassemia or SC on hemoglobin electrophoresis).
- Symptomatic SCD while on 6 months of HU OR symptomatic SCD and intolerant of HU (unable or unwilling to take HU due to hematological or other toxicities). Symptomatic SCD is defined as having one of following:
- Subject is in his/her steady state and not amidst any acute complication due to SCD (i.e., hospitalization, acute pain, or acute chest syndrome in the past 14 days).
Key exclusion criteria (20 listed)
- Inability to give informed consent.
- Experienced severe sepsis or septic shock within the previous 12 weeks.
- Last HU dose was ingested within the previous 4 weeks.
- Currently pregnant or breast-feeding.
- Alanine aminotransferase (ALT) greater than or equal to two times (2X) the upper limit of normal or albumin <2.0 mg/dL or direct (conjugated) bilirubin greater than or equal to 1.5 mg/dl.
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 Decitabine and TetrahydrouridineAlso: Dacogen, 5-aza-2'-deoxycytydine, THUOral Decitabine and Oral Tetrahydrouridine (THU) given 1-2 hours apart on 2 consecutive days over 8 weeks | Drug | Oral Decitabine and Tetrahydrouridine |
| PlaceboAlso: WaterPlain water will be dispensed at a similar volume and in the same containers as study drug. The water placebo has a similar appearance and taste to the study drug, since the study drug is highly diluted in water. | Drug | Placebo |
Primary outcome
Non-hematologic toxicity
Time frame: 12 weeks
Toxicities will be evaluated on a weekly basis and will be classified according to their grade and relationship to study treatment. Chi-square testing will be employed to examine the difference in number of patients with grade 3 or greater non-hematologic toxicity between treatment and placebo groups.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2018.
- Derived from this study: PubMed 28880867Molokie R, Lavelle D, Gowhari M, Pacini M, Krauz L, Hassan J, Ibanez V, Ruiz MA, Ng KP, Woost P, Radivoyevitch T, Pacelli D, Fada S, Rump M, Hsieh M, Tisdale JF, Jacobberger J, Phelps M, Engel JD, Saraf S, Hsu LL, Gordeuk V, DeSimone J, Saunthararajah Y. Oral tetrahydrouridine and decitabine for non-cytotoxic epigenetic gene regulation in sickle cell disease: A randomized phase 1 study. PLoS Med. 2017 Sep 7;14(9):e1002382. doi: 10.1371/journal.pmed.1002382. eCollection 2017 Sep.
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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.
Yogen Saunthararajah, MD principal investigator
The Cleveland Clinic
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 Decitabine and Tetrahydrouridine in people with Sickle Cell Disease, run by Yogen Saunthararajah 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 10 inclusion and 20 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 11 Sep 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. Some participants in this study may receive a placebo. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Non-hematologic toxicity (time frame: 12 weeks). 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 NCT01685515, 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 11 Sep 2018.