Phase 2 Study of Montelukast for the Treatment of Sickle Cell Anemia

NCT01960413 | Completed Phase 2 Results DMC

• 1 other identifier: R01FD004117
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 2

Brief Summary

In this feasibility trial, the investigators will compare participants treated with montelukast and hydroxyurea to those treated with placebo and hydroxyurea for a total of 8 weeks.

Conditions

Sickle Cell Anemia (HbSS, or HbSβ-thalassemia0)

Outcome Measures

Primary Outcomes (1)

• Change in Soluble Vascular Cell Adhesion Molecule-1 (sVCAM)

  The primary outcome measure is based on a 30% reduction, which would be \~106 ng/ml reduction. The study was designed with 25 in each group in order to explore all three aims and potential confounders. However, if the investigators are not able to accrue 25 subjects in each arm, the investigators would still be able to detect a 30% difference in sVCAM with 17 subjects in each group. The 95% confidence interval for detecting a 30% difference is between 204 ng/ml and 290 ng/ml (or an 18-42% reduction in sVCAM). Importantly, the lower limit of the 95% confidence interval (18%) is still a clinically relevant reduction in sVCAM. Thus, if the investigators detect a 30% or larger difference in sVCAM in this study, the investigators will be assured that, based on the 95% confidence interval, these data are clinically important.

  baseline to eight weeks

Study Arms (2)

Montelukast added to Hydroxyurea

EXPERIMENTAL

Oral montelukast therapy taken daily for eight weeks with current hydroxyurea regiment

Drug: Montelukast added to Hydroxyurea

Placebo added to Hydroxyurea

PLACEBO COMPARATOR

Oral placebo taken daily for eight weeks with current hydroxyurea regiment

Drug: Placebo added to Hydroxyurea

Interventions

Montelukast added to Hydroxyurea DRUG

Montelukast added to Hydroxyurea

Placebo added to Hydroxyurea DRUG

Placebo added to Hydroxyurea

Eligibility Criteria

• Age: 16 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• )Diagnosis of HbSS, or HbSβ-thalassemia0, confirmed by hemoglobin analysis
• )Males and females age 16 years to 70 years old
• )Greater than 2 episodes of pain in the last 12 months
• )On a stable dose of hydroxyurea for at least 2 months and a stable hemoglobin

You may not qualify if:

• Judged not likely to be study compliant by his/her hematologist
• History of adverse reaction to montelukast or any of the components of montelukast
• Have used medications known to interact with montelukast such as rifampin, phenobarbital, and gemfibrozil within 4 weeks of enrollment
• Currently being treated with a leukotriene antagonist (montelukast or zileuton) or have used montelukast/zileuton within the last 60 days
• Chronic blood transfusion therapy defined as regularly scheduled transfusions.
• Hemoglobin A greater than15% on hemoglobin analysis
• Individuals with a current physician diagnosis of asthma (within last 12 months) or requires continuous supplemental oxygen, or predicted or current use of asthma medications (inhaled corticosteroids, but participants taking bronchodilators will be allowed to participate).
• Current participation in another therapeutic trial for SCD
• Known current pregnancy
• Known history of HIV
• Serum creatinine greater than 3 times the site's upper limit of normal

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• Medical College of Wisconsin: collaborator
• Versiti Blood Health: collaborator

Study Sites (2)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232-9000, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• Field JJ, Kassim A, Brandow A, Embury SH, Matsui N, Wilkerson K, Bryant V, Zhang L, Simpson P, DeBaun MR. Phase 2 trial of montelukast for prevention of pain in sickle cell disease. Blood Adv. 2020 Mar 24;4(6):1159-1165. doi: 10.1182/bloodadvances.2019001165.

  PMID: 32208487 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell

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

Results Point of Contact

• Title: Michael DeBaun, MD MPH
• Organization: Vanderbilt University Medical Center

m.debaun@vumc.org

(615) 875-3040

Study Officials

• Michael R. DeBaun, MD, MPH

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

• Joshua Field, MD, MS

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics and Medicine, JC Peterson Endowed Chair in Pediatrics, Vice Chair for Clinical Research in Pediatrics, Director, Vanderbilt-Meharry-Matthew Walker Center for Excellence in Sickle Cell Disease

Study Record Dates

• First Submitted: October 8, 2013
• First Posted: October 10, 2013
• Study Start: November 1, 2013
• Primary Completion: March 1, 2018
• Study Completion: March 1, 2018
• Last Updated: March 26, 2019
• Results First Posted: March 26, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 9 months and ending 36 months following article publication
• Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose.

Locations

US (2)