A Study of Nicotinamide With Oral Tetrahydrouridine and Decitabine to Treat High Risk Sickle Cell Disease
Primary Purpose
Sickle Cell Disease
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Nicotinamide
Sponsored by
About this trial
This is an interventional treatment trial for Sickle Cell Disease
Eligibility Criteria
Inclusion Criteria:
- Age 18 years or older.
- Written informed consent provided by the subject before study entry.
- Confirmed sickle cell disease (SCD) as determined by hemoglobin electrophoresis or liquid chromatography.
- Subject is in his/her steady state and not having any acute complication due to SCD (i.e., hospitalization, acute pain, or acute chest syndrome in the past 14 days).
- Weight at least 40kg
- Regular compliance with comprehensive care and previous therapy.
- Symptomatic SCD is defined as having one of following, despite at least 6 months of hydroxyurea therapy, or refuse to take hydroxyurea for personal reasons: fetal hemoglobin <0.5 g/dL, or 3 or more pain episodes per year requiring parenteral narcotics, or 1 or more acute chest syndrome episodes, or Hemoglobin <9 g/dL and absolute reticulocyte count <250,000/mm3.
Exclusion Criteria:
- 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) ≥ 3 times the upper limit of normal or albumin <2.0 mg/dL or direct (conjugated) bilirubin ≥ 1.5 mg/dl.
- Serum creatinine >2.9 mg/dL and calculated creatinine clearance <30 mL/min.
- 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: (i) not having heterosexual sexual contact beginning at the screening visit and continuing until 4 weeks after the last dose of 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 and 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 known Myelodysplastic syndrome, leukemia, or an abnormal karyotype.
- New York Heart Association (NYHA) class III/IV status.
- Eastern Co-operative Oncology Group (ECOG) performance status ≥3.
- Participant is on chronic transfusion therapy
- Known history of illicit drug or alcohol abuse within the past 12 months.
- Other experimental or investigational drug therapy in the past 28 days.
- Taking l-glutamine within the last 28 days
- Being positive for HIV infection
Sites / Locations
- University of Illinois at Chicago College of MedicineRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Nicotinamide
THU Decitabine
Arm Description
Oral Nicotinamide 1000 mg twice daily
Oral 250 mg THU and 5 mg decitabine Once per week
Outcomes
Primary Outcome Measures
Blood Hemoglobin
Measure hemoglobin function
Secondary Outcome Measures
Full Information
NCT ID
NCT04055818
First Posted
August 12, 2019
Last Updated
April 4, 2023
Sponsor
EpiDestiny, Inc.
Collaborators
National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
1. Study Identification
Unique Protocol Identification Number
NCT04055818
Brief Title
A Study of Nicotinamide With Oral Tetrahydrouridine and Decitabine to Treat High Risk Sickle Cell Disease
Official Title
Proof-of-concept Study of Nicotinamide and Oral Tetrahydrouridine (THU) and Decitabine to Treat High Risk Sickle Cell Disease
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 24, 2020 (Actual)
Primary Completion Date
March 8, 2024 (Anticipated)
Study Completion Date
April 5, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
EpiDestiny, Inc.
Collaborators
National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
A randomized control trial in 20 subjects with sickle cell disease comparing oral THU-decitabine to nicotinamide and in combination (THU, decitabine and nicotinamide).
Detailed Description
A randomized control trial comparing oral THU-decitabine to nicotinamide (1:1 randomization), and then comparing the effects of the combination of nicotinamide with THU-decitabine vs either treatment alone. Treatment with each agent alone is for 12 weeks followed by the combination for a further 12 weeks. Patients have the option to enter an extension phase of combination treatment for an additional 24 weeks (total of 48 weeks)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
1:1 Randomization
Masking
None (Open Label)
Allocation
Randomized
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Nicotinamide
Arm Type
Experimental
Arm Description
Oral Nicotinamide 1000 mg twice daily
Arm Title
THU Decitabine
Arm Type
Experimental
Arm Description
Oral 250 mg THU and 5 mg decitabine Once per week
Intervention Type
Drug
Intervention Name(s)
Nicotinamide
Other Intervention Name(s)
Decitabine, Tetrahydrouridine
Intervention Description
Oral nicotinamide (Vitamin B3) alone compared to THU Decitabine combination
Primary Outcome Measure Information:
Title
Blood Hemoglobin
Description
Measure hemoglobin function
Time Frame
12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 18 years or older.
Written informed consent provided by the subject before study entry.
Confirmed sickle cell disease (SCD) as determined by hemoglobin electrophoresis or liquid chromatography.
Subject is in his/her steady state and not having any acute complication due to SCD (i.e., hospitalization, acute pain, or acute chest syndrome in the past 14 days).
Weight at least 40kg
Regular compliance with comprehensive care and previous therapy.
Symptomatic SCD is defined as having one of following, despite at least 6 months of hydroxyurea therapy, or refuse to take hydroxyurea for personal reasons: fetal hemoglobin <0.5 g/dL, or 3 or more pain episodes per year requiring parenteral narcotics, or 1 or more acute chest syndrome episodes, or Hemoglobin <9 g/dL and absolute reticulocyte count <250,000/mm3.
Exclusion Criteria:
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) ≥ 3 times the upper limit of normal or albumin <2.0 mg/dL or direct (conjugated) bilirubin ≥ 1.5 mg/dl.
Serum creatinine >2.9 mg/dL and calculated creatinine clearance <30 mL/min.
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: (i) not having heterosexual sexual contact beginning at the screening visit and continuing until 4 weeks after the last dose of 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 and 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 known Myelodysplastic syndrome, leukemia, or an abnormal karyotype.
New York Heart Association (NYHA) class III/IV status.
Eastern Co-operative Oncology Group (ECOG) performance status ≥3.
Participant is on chronic transfusion therapy
Known history of illicit drug or alcohol abuse within the past 12 months.
Other experimental or investigational drug therapy in the past 28 days.
Taking l-glutamine within the last 28 days
Being positive for HIV infection
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lani Krauz
Phone
312-413-0242
Email
LIgnacio@UIC.EDU
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Molokie
Organizational Affiliation
University of Illinois at Chicago College of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Illinois at Chicago College of Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lani Krauz
Phone
312-413-0242
Email
Llgnacio@UIC.EDU
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study of Nicotinamide With Oral Tetrahydrouridine and Decitabine to Treat High Risk Sickle Cell Disease
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