A Study of Nicotinamide With Oral Tetrahydrouridine and Decitabine to Treat High Risk Sickle Cell Disease

NCT04055818 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 2019-0631
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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).

Conditions

Sickle Cell Disease

Outcome Measures

Primary Outcomes (1)

• Blood Hemoglobin

  Measure hemoglobin function

  12 weeks

Study Arms (2)

Nicotinamide

EXPERIMENTAL

Oral Nicotinamide 1000 mg twice daily

Drug: Nicotinamide

THU Decitabine

EXPERIMENTAL

Oral 250 mg THU and 5 mg decitabine Once per week

Drug: Nicotinamide

Interventions

Nicotinamide DRUG

Oral nicotinamide (Vitamin B3) alone compared to THU Decitabine combination

Also known as: Decitabine, Tetrahydrouridine

Nicotinamide; THU Decitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• EpiDestiny, Inc.: lead
• National Institutes of Health (NIH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Illinois at Chicago College of Medicine

Chicago, Illinois, 60612, United States

RECRUITING

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Niacinamide; Decitabine; Tetrahydrouridine

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Uridine

Study Officials

• Robert Molokie

  University of Illinois at Chicago College of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lani Krauz

CONTACT

312-413-0242; LIgnacio@UIC.EDU

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 1:1 Randomization

Study Record Dates

• First Submitted: August 12, 2019
• First Posted: August 14, 2019
• Study Start: January 24, 2020
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): April 30, 2027
• Last Updated: May 25, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)