Assessment of Algorithm-Based Hydroxyurea Dosing on Fetal Hemoglobin Response, Acute Complications, and Organ Function in People With Sickle Cell Disease

NCT02225132 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 14017214-H-0172
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Sickle cell disease (SCD) is a blood disease. The drug hydroxyurea (HU) is approved to prevent pain crises in people with SCD. Researchers want to see how higher doses of HU affect the blood. This will help them learn about the right dosage of HU to give to people with SCD. Objective: \- To improve hydroxyurea dosing in people with SCD. Eligibility: \- People age 15 or older with homozygous SCD (HbSS). Design:

• Participants will be screened with medical history, physical exam, medication review, and blood and urine tests.
• Participants will be in the study for about 15 months.
• First 3 months: monthly study visits with blood and urine tests.
• After 3 months: participants will take HU as a capsule by mouth. If you are already taking HU, your dose will be increased.
• Within a month of starting or increasing HU: participants will keep a daily pain diary for 2 weeks. They will have an echocardiogram (ultrasound) of the heart, a 6-minute walk test. They will complete a quality-of-life questionnaire.
• Participants will visit every month until they reach their highest tolerated dose of HU. They may need to come as often as every week sometimes to closely monitor their blood counts. Then they will alternate a phone call one month and a visit the next. At the visits, participants will bring their pill bottle, answer questions about side effects, and have blood tests.
• Every 2 months, participants will have a medical history, physical exam, and blood tests.
• Every 4 months, participants will have blood and urine tests. They will also complete another 2-week pain diary and quality-of-life questionnaire.
• About 12 months after starting or increasing HU, participants will have blood tests, an echocardiogram, and a 6-minute walk test.

Conditions

Sickle Cell Disease

Keywords

Hydroxyurea; Sickle Cell Disease; Fetal Hemoglobin Induction

Outcome Measures

Primary Outcomes (2)

• Fetal Hemoglobin Level

  Mean fetal hemoglobin calculated to indicate effectiveness of hydroxyurea dose

  Baseline

• Fetal Hemoglobin Level

  Mean fetal hemoglobin calculated to indicate effectiveness of hydroxyurea dose

  12 months

Study Arms (1)

1

EXPERIMENTAL

This is a one arm, open-label, non- randomized pilot study to evaluate the effect of algorithm- based HU dosing on the HbF response, the ability to titrate each patient to the MTD of HU, acute complications, and organ function in patients with HbSS.

Drug: Hydroxyurea

Interventions

Hydroxyurea DRUG

The precise mechanism by which hydroxyurea produces its cytotoxic and cytoreductive effects is not known. However, various studies support the hypothesis that hydroxyurea causes an immediate inhibition of DNA synthesis by acting as a ribonucleotide reductase inhibitor, without interfering with the synthesis of ribonucleic acid or of protein. The mechanisms by which DROXIA produces its beneficial effects in patients with sickle cell anemia (SCA) are uncertain. Known pharmacologic effects of DROXIA that may contribute to its beneficial effects include increasing hemoglobin F levels in RBCs, decreasing neutrophils, increasing the water content of RBCs, increasing deformability of sickled cells, and altering the adhesion of RBCs to endothelium.

1

Eligibility Criteria

• Age: 15 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age greater than or equal to 15 years
• Homozygous sickle cell disease (HbSS)
• Patients with recent transfusion must have HbA \<15% prior to enrollment
• ANC greater than or equal to 2,000/microL, platelets greater than or equal to150,000/microL, Hb \> 5.4g/dL, and ARC greater than or equal to100,000/microL (unless the Hb is \> 8g/dL) at baseline
• Patients on angiotensin-converting enzyme inhibitors and angiotensin receptor blockers should be on a stable dose for 2 weeks prior to initiating or adjusting HU

You may not qualify if:

• Pregnant or lactating women or patients planning to get pregnant during the study period
• Patients unwilling to use two forms of contraception throughout the period of HU administration
• Patients receiving chronic transfusion therapy
• Patients receiving a HU dose of greater than or equal to 20 mg/kg/day
• Patients with history of allergy or intolerance to HU judged by the investigator to be prohibitive against restarting HU
• Patients with end stage renal disease defined as GFR \<10mL/min/1.73m(2)
• \. Patients being treated with antiretroviral agents (such as didanosine and stavudine) because of a higher risk for potentially fatal pancreatitis, hepatic failure, hepatitis, and severe peripheral neuropathy when co-administered with hydroxyurea.
• \. Participation on any other chronic investigative treatment studies
• \. Unable to understand the investigational nature of the study or give informed consent.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Hydroxyurea

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)

Urea; Amides; Organic Chemicals

Results Point of Contact

• Title: Fitzhugh, Courtney
• Organization: National Heart Lung and Blood Institute

courtney.fitzhugh@nih.gov

+1 301 402 6496

Study Officials

• Courtney D Fitzhugh, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2014
• First Posted: August 26, 2014
• Study Start: August 23, 2014
• Primary Completion: May 24, 2018
• Study Completion: May 24, 2018
• Last Updated: August 6, 2019
• Results First Posted: August 6, 2019

Record last verified: 2019-04-25

Locations

US (1)