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

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ClinicalTrials.gov Identifier: NCT01960413

Recruitment Status : Completed

First Posted : October 10, 2013

Results First Posted : March 26, 2019

Last Update Posted : March 26, 2019

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborators:

Medical College of Wisconsin

Versiti

Information provided by (Responsible Party):

Michael DeBaun, Vanderbilt University Medical Center

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
Condition	Sickle Cell Anemia (HbSS, or HbSβ-thalassemia0)
Interventions	Drug: Montelukast added to Hydroxyurea Drug: Placebo added to Hydroxyurea
Enrollment	46

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Montelukast Added to Hydroxyurea	Placebo Added to Hydroxyurea
Arm/Group Description	Oral montelukast therapy taken dail...	Oral placebo taken daily for eight ...
Arm/Group Description	Oral montelukast therapy taken daily for eight weeks with current hydroxyurea regiment Montelukast added to Hydroxyurea	Oral placebo taken daily for eight weeks with current hydroxyurea regiment Placebo added to Hydroxyurea
Period Title: Overall Study
Started	24	22
Completed	20	21
Not Completed	4	1
Reason Not Completed
Withdrawal by Subject	1	1
Physician Decision	1	0
Lost to Follow-up	2	0

Baseline Characteristics

Arm/Group Title		Montelukast Added to Hydroxyurea	Placebo Added to Hydroxyurea	Total
Arm/Group Description		Oral montelukast therapy taken dail...	Oral placebo taken daily for eight ...	Total of all reporting groups
Arm/Group Description		Oral montelukast therapy taken daily for eight weeks with current hydroxyurea regiment Montelukast added to Hydroxyurea	Oral placebo taken daily for eight weeks with current hydroxyurea regiment Placebo added to Hydroxyurea	Total of all reporting groups
Overall Number of Baseline Participants		24	22	46
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	24 participants	22 participants	46 participants
		29.25 (10.46)	30.76 (10.24)	29.95 (10.27)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	24 participants	22 participants	46 participants
	Female	13 54.2%	14 63.6%	27 58.7%
	Male	11 45.8%	8 36.4%	19 41.3%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	24 participants	22 participants	46 participants
	Hispanic or Latino	0 0.0%	0 0.0%	0 0.0%
	Not Hispanic or Latino	23 95.8%	22 100.0%	45 97.8%
	Unknown or Not Reported	1 4.2%	0 0.0%	1 2.2%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	24 participants	22 participants	46 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	24 100.0%	18 81.8%	42 91.3%
	White	0 0.0%	1 4.5%	1 2.2%
	More than one race	0 0.0%	3 13.6%	3 6.5%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment Measure Type: Number Unit of measure: Participants
United States	Number Analyzed	24 participants	22 participants	46 participants
United States		24	22	46

Outcome Measures

1.Primary Outcome


Title	Change in Soluble Vascular Cell Adhesion Molecule-1 (sVCAM)
Description	The primary outcome measure is based on a 30% reduction, which would b...
Description	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.
Time Frame	baseline to eight weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Montelukast Added to Hydroxyurea	Placebo Added to Hydroxyurea
Arm/Group Description:	Oral montelukast therapy taken dail...	Oral placebo taken daily for eight ...
Arm/Group Description:	Oral montelukast therapy taken daily for eight weeks with current hydroxyurea regiment Montelukast added to Hydroxyurea	Oral placebo taken daily for eight weeks with current hydroxyurea regiment Placebo added to Hydroxyurea
Overall Number of Participants Analyzed	20	21
Median (Inter-Quartile Range) Unit of Measure: ng/mL
	-3.2 (-13.6 to 11.6)	4.17 (-3.3 to 12.1)

Adverse Events

Time Frame	8 weeks
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Montelukast Added to Hydroxyurea		Placebo Added to Hydroxyurea
Arm/Group Description	Oral montelukast therapy taken dail...		Oral placebo taken daily for eight ...
Arm/Group Description	Oral montelukast therapy taken daily for eight weeks with current hydroxyurea regiment Montelukast added to Hydroxyurea		Oral placebo taken daily for eight weeks with current hydroxyurea regiment Placebo added to Hydroxyurea
All-Cause Mortality
	Montelukast Added to Hydroxyurea		Placebo Added to Hydroxyurea
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/24 (0.00%)		0/22 (0.00%)
Serious Adverse Events Serious Adverse Events
	Montelukast Added to Hydroxyurea		Placebo Added to Hydroxyurea
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/24 (16.67%)		2/22 (9.09%)
Blood and lymphatic system disorders
Pain ^† [1]	2/24 (8.33%)	2	2/22 (9.09%)	2
Acute Chest Syndrome ^†	2/24 (8.33%)	2	0/22 (0.00%)	0
† Indicates events were collected by systematic assessment [1] Sickle Cell Pain Crisis/Acute Chest Syndrome
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Montelukast Added to Hydroxyurea		Placebo Added to Hydroxyurea
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/24 (41.67%)		12/22 (54.55%)
Blood and lymphatic system disorders
Pain ^†	3/24 (12.50%)	4	6/22 (27.27%)	9
Cardiac disorders
systolic murmur ^†	1/24 (4.17%)	1	0/22 (0.00%)	0
Ear and labyrinth disorders
ear injury ^†	0/24 (0.00%)		1/22 (4.55%)	2
Eye disorders
scleral disorder ^†	1/24 (4.17%)	1	0/22 (0.00%)	0
Gastrointestinal disorders
diarrhea ^†	1/24 (4.17%)	1	2/22 (9.09%)	3
stomach pain ^†	1/24 (4.17%)	1	0/22 (0.00%)	0
General disorders
headache ^†	0/24 (0.00%)		1/22 (4.55%)	1
Infections and infestations
pharyngitis ^†	1/24 (4.17%)	1	0/22 (0.00%)	0
flu like symptoms ^†	0/24 (0.00%)	0	0/22 (0.00%)	0
Breast Infection ^†	0/24 (0.00%)	0	1/22 (4.55%)	1
Injury, poisoning and procedural complications
Injury,laceration ^†	0/24 (0.00%)	0	1/22 (4.55%)	1
Pain ^†	3/24 (12.50%)	3	2/22 (9.09%)	2
Nervous system disorders
headache, migraine ^†	0/24 (0.00%)	0	1/22 (4.55%)	2
Renal and urinary disorders
urinary frequency ^†	1/24 (4.17%)	1	0/22 (0.00%)	0
Reproductive system and breast disorders
vaginal discharge ^†	1/24 (4.17%)	1	0/22 (0.00%)	0
penile pain/priapsm ^†	1/24 (4.17%)	1	1/22 (4.55%)	1
Respiratory, thoracic and mediastinal disorders
cough ^†	0/24 (0.00%)	0	1/22 (4.55%)	1
Pain ^†	1/24 (4.17%)	1	0/22 (0.00%)	0
sore throat ^†	1/24 (4.17%)	1	0/22 (0.00%)	0
nasal congestion ^†	0/24 (0.00%)	0	1/22 (4.55%)	1
upper respiratory infection ^†	2/24 (8.33%)	2	2/22 (9.09%)	2
dyspnea ^†	1/24 (4.17%)	1	0/22 (0.00%)	0
pain,dyspnea ^†	1/24 (4.17%)	1	0/22 (0.00%)	0
productive cough ^†	1/24 (4.17%)	2	0/22 (0.00%)	0
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Michael DeBaun, MD MPH
Organization:	Vanderbilt University Medical Center
Phone:	(615) 875-3040
EMail:	m.debaun@vumc.org

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Layout table for additonal information

Responsible Party:	Michael DeBaun, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier:	NCT01960413
Other Study ID Numbers:	R01FD004117 ( U.S. FDA Grant/Contract )
First Submitted:	October 8, 2013
First Posted:	October 10, 2013
Results First Submitted:	March 7, 2019
Results First Posted:	March 26, 2019
Last Update Posted:	March 26, 2019

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