Treatment for high-risk sickle cell disease using nicotinamide and other medications

Proof-of-concept Study of Nicotinamide and Oral Tetrahydrouridine (THU) and Decitabine to Treat High Risk Sickle Cell Disease

This study is testing if a combination of three medications can help people with high-risk sickle cell disease feel better and manage their symptoms more effectively.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: EpiDestiny, Inc. (Industry-sponsored)
• Locations: 1 site (Chicago, Illinois)
• Trial ID: NCT04055818 on ClinicalTrials.gov

What this trial studies

This clinical trial is a randomized control study involving 20 subjects with sickle cell disease. It compares the effects of oral tetrahydrouridine (THU) combined with decitabine to nicotinamide, as well as the combination of all three treatments. Each treatment will be administered for 12 weeks, followed by an additional 12 weeks of combination therapy, with an option for participants to extend the combination treatment for another 24 weeks. The aim is to evaluate the efficacy and safety of these treatments in managing high-risk sickle cell disease.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with confirmed sickle cell disease who have not experienced acute complications in the past 14 days.

Not a fit: Patients who are unable to provide informed consent or have had severe sepsis or septic shock recently may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the management of high-risk sickle cell disease and reduce complications.

How similar studies have performed: While this approach is novel, similar studies have shown promise in exploring combination therapies 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

Where this trial is running

Chicago, Illinois

• University of Illinois at Chicago College of Medicine — Chicago, Illinois, United States (Recruiting)

Study contacts

• Principal investigator: Robert Molokie — University of Illinois at Chicago College of Medicine
• Study coordinator: Lani Krauz

Conditions Sickle Cell Disease