Sickle Cell Anemia (HbSS, or HbSβ-thalassemia0)Phase 2NCT01960413
Phase 2 Study of Montelukast for the Treatment of Sickle Cell Anemia
A Phase 2 study testing Montelukast added to Hydroxyurea in people with Sickle Cell Anemia (HbSS, or HbSβ-thalassemia0), run by Vanderbilt University Medical Center at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 to 70 years
- Conditions the study is for
- Sickle Cell Anemia (HbSS, or HbSβ-thalassemia0)
- What is being tested?
- Montelukast added to Hydroxyurea
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 46 participants
- Where
- 2 sitesUnited States
- Study dates
- Nov 2013to Mar 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 1)Diagnosis of HbSS, or HbSβ-thalassemia0, confirmed by hemoglobin analysis
- 2)Males and females age 16 years to 70 years old
- 3)Greater than 2 episodes of pain in the last 12 months
- 4)On a stable dose of hydroxyurea for at least 2 months and a stable hemoglobin
Who cannot join
- 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
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- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Vanderbilt University Medical Center
Nashville, Tennessee, 37232-9000
About this study
Official title: Phase 2 Study of Montelukast for the Treatment of Sickle Cell Anemia (Also Known as the Montelukast Trial in Sickle Cell Anemia)
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.
Read the detailed description
The primary hypothesis for this trial is that montelukast adds efficacy to hydroxyurea therapy for improving vaso-occlusion when compared to hydroxyurea alone. The following specific aims will be tested in adolescents and adults with sickle cell disease (SCD):
Aim 1. To determine whether montelukast versus placebo added to hydroxyurea will improve markers of vaso-occlusion-associated tissue injury in adolescents and adults with sickle cell disease.
Aim 2. To evaluate physiologic effects of montelukast versus placebo added to hydroxyurea in adolescents and adults with sickle cell disease.
Subaim 2A. To determine if montelukast versus placebo added to hydroxyurea will improve lung function in adolescents and adults with sickle cell disease.
Subaim 2B. To determine if montelukast versus placebo added to hydroxyurea will improve forearm microvascular blood flow in adolescents and adults with sickle cell disease, respectively.
Funding Source - FDA OOPD
- Being tested
- Montelukast added to Hydroxyurea, Placebo added to Hydroxyurea
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Montelukast added to HydroxyureaDrug
Placebo added to HydroxyureaDrug
| Study group | Role | What they receive |
|---|---|---|
| Montelukast added to Hydroxyurea | Experimental | Oral montelukast therapy taken daily for eight weeks with current hydroxyurea regiment Receives: Drug: Montelukast added to Hydroxyurea |
| Placebo added to Hydroxyurea | Placebo comparator | Oral placebo taken daily for eight weeks with current hydroxyurea regiment Receives: Drug: Placebo added to Hydroxyurea |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: baseline to eight weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2013 (estimated)
- Study startNov 2013
- Primary completionMar 2018
- Study completionMar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell Anemia (HbSS, or HbSβ-thalassemia0)Studies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Medical College of Wisconsin, Versiti Blood Health
- Responsible party
- Principal investigator, Michael DeBaun, Vanderbilt University Medical Center
- Investigators
- Michael R. DeBaun, MD, MPH, Principal investigator, Vanderbilt University Medical CenterJoshua Field, MD, MS, Principal investigator, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01960413
- Sponsor's protocol ID
- R01FD004117
- Status last verified
- Mar 2019
- First submitted
- 8 Oct 2013
- Last updated
- 26 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices)
Publications
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.
PubMed 32208487
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Study of Montelukast for the Treatment of Sickle Cell Anemia (Also Known as the Montelukast Trial in Sickle Cell Anemia)
- ClinicalTrials.gov ID
- NCT01960413
- Acronym / sponsor ID
- R01FD004117
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Collaborators
- Medical College of Wisconsin, Versiti Blood Health
- Study start
- Nov 2013
- Primary completion
- Mar 2018 (actual)
- Study completion
- Mar 2018 (actual)
- First posted
- 10 Oct 2013 (estimated)
- Results
- Posted 26 Mar 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The primary hypothesis for this trial is that montelukast adds efficacy to hydroxyurea therapy for improving vaso-occlusion when compared to hydroxyurea alone. The following specific aims will be tested in adolescents and adults with sickle cell disease (SCD):
Aim 1. To determine whether montelukast versus placebo added to hydroxyurea will improve markers of vaso-occlusion-associated tissue injury in adolescents and adults with sickle cell disease.
Aim 2. To evaluate physiologic effects of montelukast versus placebo added to hydroxyurea in adolescents and adults with sickle cell disease.
Subaim 2A. To determine if montelukast versus placebo added to hydroxyurea will improve lung function in adolescents and adults with sickle cell disease.
Subaim 2B. To determine if montelukast versus placebo added to hydroxyurea will improve forearm microvascular blood flow in adolescents and adults with sickle cell disease, respectively.
Funding Source - FDA OOPD
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Montelukast added to Hydroxyurea | Experimental | Drug: Montelukast added to HydroxyureaOral montelukast therapy taken daily for eight weeks with current hydroxyurea regiment |
| Placebo added to Hydroxyurea | Placebo comparator | Drug: Placebo added to HydroxyureaOral placebo taken daily for eight weeks with current hydroxyurea regiment |
Who may qualify
- Ages
- 16 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 1)Diagnosis of HbSS, or HbSβ-thalassemia0, confirmed by hemoglobin analysis
- 2)Males and females age 16 years to 70 years old
- 3)Greater than 2 episodes of pain in the last 12 months
- 4)On a stable dose of hydroxyurea for at least 2 months and a stable hemoglobin
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Montelukast added to Hydroxyurea | Drug | Montelukast added to Hydroxyurea |
| Placebo added to Hydroxyurea | Drug | Placebo added to Hydroxyurea |
Primary outcome
Change in Soluble Vascular Cell Adhesion Molecule-1 (sVCAM)
Time frame: baseline to eight weeks
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32208487Field 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.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices)
Related trials for Sickle Cell Anemia (HbSS, or HbSβ-thalassemia0)
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Buprenorphine for the Management of Pain in Children With Sickle Cell Disease
Sickle Cell Disease (SCD), Sickle Cell Disease Vaso-occlusive Crisis
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Hypoxic Red Blood Cells in Sickle Cell Anemia
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Sickle Cell Anemia (HbSS, or HbSβ-thalassemia0), Albuminuria
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Hematopoietic Stem Cell BCL11A Enhancer Gene Editing for Severe β-Hemoglobinopathies
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael R. DeBaun, MD, MPH principal investigator
Vanderbilt University Medical Center
Joshua Field, MD, MS principal investigator
Medical College of Wisconsin
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Montelukast added to Hydroxyurea in people with Sickle Cell Anemia (HbSS, or HbSβ-thalassemia0), run by Vanderbilt University Medical Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Mar 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Soluble Vascular Cell Adhesion Molecule-1 (sVCAM) (time frame: baseline to eight weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01960413, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2019.