AsthmaTPORTNCT00513760
Transporter Mediated Uptake of Montelukast
A study testing Grapefruit juice, Orange Juice and Gatorade in people with Asthma, run by Nemours Children's Clinic at 1 site in United States.
Trial summary
Leukotriene receptor antagonists (LTRAs) are frequently prescribed to reduce the symptoms associated with asthma. Singulair, manufactured by Merck, is a popular LTRA, however its effectiveness varies greatly between individuals. We are interested in understanding why the effectiveness of Singulair varies so greatly. Read more about this study
- Who is it for?
- Ages 15 to 18 years
- Conditions the study is for
- Asthma
- What is being tested?
- Grapefruit juice, Orange Juice and Gatorade
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2007to Dec 2014
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 15 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Doctor diagnosed asthma.
- Must not be taking any medications except for inhaled steroids.
Who cannot join
- Clinical conditions other than asthma.
- Upper respiratory tract infection within the past 30 days.
- Gastrointestinal conditions.
- Unable to stop taking or are required to begin taking any type of oral medication for the duration of the trial
Trial locations and contacts
1 site in 1 country.
United States1 site
Nemours Children's Clinic
Jacksonville, Florida, 32207
About this study
Official title: Characterization of Transporter Mediated Uptake of Montelukast in Humans
Leukotriene receptor antagonists (LTRAs) are frequently prescribed to reduce the symptoms associated with asthma. Singulair, manufactured by Merck, is a popular LTRA, however its effectiveness varies greatly between individuals. We are interested in understanding why the effectiveness of Singulair varies so greatly.
For an oral drug such as Singulair to be effective, the body must efficiently absorb it. We have found that blood levels of Singulair vary greatly between individuals, and we think that this variability is responsible for variability in response.
Read more
Drug absorption occurs primarily in the intestine. Due to differences in the chemical properties of drugs, some drugs can be absorbed easily while other drugs require help from special proteins produced by the cells that line the intestine. These proteins, or transporters act like turnstiles to allow drugs to move from the intestine to the bloodstream and are known to be inhibited by components of citrus juice. The activity of a transporter can be influenced by individual genetic variability.
We think that Singulair requires help from a transport protein to be absorbed and that genetic variability in this transporter leads to variability in the blood level of Singulair. In this proposal we will use citrus juice (grapefruit and orange) to inhibit intestinal membrane transport proteins and show that Singulair requires these transporters to be efficiently absorbed. Eventually, what we learn from this work will allow doctors to quickly test individuals with asthma to determine how well they will absorb Singulair and possibly other LTRAs. Knowing this will allow the doctor to adjust the drug treatment on an individual basis to maximize benefit in the treatment of asthma.
Read the detailed description
Montelukast (Merck brand name Singulair) is a selective Cys-LT1 receptor antagonist that is used to control asthma symptoms in children and adults. Although safe and effective, the inter-patient variability in response is substantial (25-60% response rate), which is due in part to genetic variability. For example, we recently reported that polymorphisms in candidate genes that encode proteins in the LT pathway influence responsiveness to the drug.
The long-range goal of our studies is to determine the contribution of genetic variability to the inter-patient variability in montelukast blood levels and responsiveness. In preliminary studies, we found that the plasma concentration vs. time data in single and multiple dose-studies vary more than 10-fold, which could contribute to inter-patient variability in response.
Montelukast is about 64% bioavailable, is cleared by CYP2C9 and CYP3A4 in the liver, and is nearly completely excreted into the bile. The physical properties of montelukast suggest that the drug undergoes transport by solute carrier transporters (SLC family transporters) and/or ATP-binding cassette transporters (ABC family transporters). Recent studies support the idea that genetic variation in genes encoding SLC and ABC transporters can influence the pharmacokinetics of drugs that are substrates for these transporters.
In the present submission, we propose to determine if montelukast is a substrate for SLC and/or ABC transporters. To accomplish this we will coadminister Singulair with citrus juice which contains known inhibitors of membrane transport proteins. If transporters are involved in the absorption of montelukast, then citrus juice should decrease the absorption of montelukast relative to Gatorade. Our working hypothesis for this study is that montelukast is a substrate for SLC (OATP1B3, OATP1B1, OATP2B1, OATP1A2) and ABC (MRP1, MRP2, and MRP3, BCRP) transporters. If true, then the pharmacokinetics of montelukast will be determined by the genetics of the membrane transporters. This highly significant observation will have important implications for understanding the disposition of montelukast in patients, and ultimately will lead to individualization of montelukast therapy in asthma.
- Conditions
- Asthma
- Being tested
- Grapefruit juice, Orange Juice, Gatorade
- Keywords
- Pharmacogenetics, Singulair, montelukast, Leukotriene Antagonists, Anti-Asthmatic Agents, Intestinal Absorption, pharmacokinetics, absorption, biochemical transport, Membrane Transport Proteins, Drug Interactions
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Grapefruit juiceDietary supplement
Also called Brand: Great Value frozen concentrated grapefruit juice(Walmart).
Coingestion of 240 ml of grapefruit juice with 10 mg of montelukast.
Orange JuiceDietary supplement
Also called Brand: Winn Dixie orange juice (Winn Dixie).
Coingestion of 240 ml of orange juice with 10 mg of montelukast.
GatoradeDietary supplement
Also called Brand: Gatorade Rain.
Coingestion of 240 ml of Gatorade with 10 mg of montelukast.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Coingestion of 240 ml of grapefruit juice with 10 mg of montelukast. Receives: Dietary Supplement: Grapefruit juice |
| 2 | Active comparator | Coingestion of 240 ml of orange juice with 10 mg of montelukast. Receives: Dietary Supplement: Orange Juice |
| 3 | Placebo comparator | Coingestion of 240 ml of Gatorade with 10 mg of montelukast. Receives: Dietary Supplement: Gatorade |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the concentration vs. time curve for the serum concentration of montelukast when coingested with grapefruit juice, orange juice, or Gatorade.
Measured: Within 12 hours after administration of a single 10 mg dose.
Secondary outcomes (1)
Improvement in respiratory function as assessed by spirometry, and impulse oscillometry vs. serum concentration of montelukast.
Measured: Within 12 hours after administration of a single 10 mg dose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2007 (estimated)
- Study startJun 2007
- Primary completionSep 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nemours Children's Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Edward Mougey, Nemours Children's Clinic
- Investigators
- Edward B Mougey, Ph.D., Principal investigator, Nemours Children's Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00513760
- Sponsor's protocol ID
- 32711
- Other IDs
- 32-03215-003
- Acronym
- TPORT
- Status last verified
- Feb 2025
- First submitted
- 7 Aug 2007
- Last updated
- 10 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
Publications
Lima JJ. Treatment heterogeneity in asthma: genetics of response to leukotriene modifiers. Mol Diagn Ther. 2007;11(2):97-104. doi: 10.1007/BF03256228.
PubMed 17397245Lima JJ, Zhang S, Grant A, Shao L, Tantisira KG, Allayee H, Wang J, Sylvester J, Holbrook J, Wise R, Weiss ST, Barnes K. Influence of leukotriene pathway polymorphisms on response to montelukast in asthma. Am J Respir Crit Care Med. 2006 Feb 15;173(4):379-85. doi: 10.1164/rccm.200509-1412OC. Epub 2005 Nov 17.
PubMed 16293801
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterization of Transporter Mediated Uptake of Montelukast in Humans
- ClinicalTrials.gov ID
- NCT00513760
- Acronym / sponsor ID
- TPORT / 32711
- Conditions
- Asthma
- Keywords
- Pharmacogenetics, Singulair, montelukast, Leukotriene Antagonists, Anti-Asthmatic Agents, Intestinal Absorption, pharmacokinetics, absorption
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Nemours Children's ClinicUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Jun 2007
- Primary completion
- Sep 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 9 Aug 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Leukotriene receptor antagonists (LTRAs) are frequently prescribed to reduce the symptoms associated with asthma. Singulair, manufactured by Merck, is a popular LTRA, however its effectiveness varies greatly between individuals. We are interested in understanding why the effectiveness of Singulair varies so greatly.
For an oral drug such as Singulair to be effective, the body must efficiently absorb it. We have found that blood levels of Singulair vary greatly between individuals, and we think that this variability is responsible for variability in response.
Drug absorption occurs primarily in the intestine. Due to differences in the chemical properties of drugs, some drugs can be absorbed easily while other drugs require help from special proteins produced by the cells that line the intestine. These proteins, or transporters act like turnstiles to allow drugs to move from the intestine to the bloodstream and are known to be inhibited by components of citrus juice. The activity of a transporter can be influenced by individual genetic variability.
We think that Singulair requires help from a transport protein to be absorbed and that genetic variability in this transporter leads to variability in the blood level of Singulair. In this proposal we will use citrus juice (grapefruit and orange) to inhibit intestinal membrane transport proteins and show that Singulair requires these transporters to be efficiently absorbed. Eventually, what we learn from this work will allow doctors to quickly test individuals with asthma to determine how well they will absorb Singulair and possibly other LTRAs. Knowing this will allow the doctor to adjust the drug treatment on an individual basis to maximize benefit in the treatment of asthma.
Detailed description
Montelukast (Merck brand name Singulair) is a selective Cys-LT1 receptor antagonist that is used to control asthma symptoms in children and adults. Although safe and effective, the inter-patient variability in response is substantial (25-60% response rate), which is due in part to genetic variability. For example, we recently reported that polymorphisms in candidate genes that encode proteins in the LT pathway influence responsiveness to the drug.
The long-range goal of our studies is to determine the contribution of genetic variability to the inter-patient variability in montelukast blood levels and responsiveness. In preliminary studies, we found that the plasma concentration vs. time data in single and multiple dose-studies vary more than 10-fold, which could contribute to inter-patient variability in response.
Montelukast is about 64% bioavailable, is cleared by CYP2C9 and CYP3A4 in the liver, and is nearly completely excreted into the bile. The physical properties of montelukast suggest that the drug undergoes transport by solute carrier transporters (SLC family transporters) and/or ATP-binding cassette transporters (ABC family transporters). Recent studies support the idea that genetic variation in genes encoding SLC and ABC transporters can influence the pharmacokinetics of drugs that are substrates for these transporters.
In the present submission, we propose to determine if montelukast is a substrate for SLC and/or ABC transporters. To accomplish this we will coadminister Singulair with citrus juice which contains known inhibitors of membrane transport proteins. If transporters are involved in the absorption of montelukast, then citrus juice should decrease the absorption of montelukast relative to Gatorade. Our working hypothesis for this study is that montelukast is a substrate for SLC (OATP1B3, OATP1B1, OATP2B1, OATP1A2) and ABC (MRP1, MRP2, and MRP3, BCRP) transporters. If true, then the pharmacokinetics of montelukast will be determined by the genetics of the membrane transporters. This highly significant observation will have important implications for understanding the disposition of montelukast in patients, and ultimately will lead to individualization of montelukast therapy in asthma.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Dietary Supplement: Grapefruit juiceCoingestion of 240 ml of grapefruit juice with 10 mg of montelukast. |
| 2 | Active comparator | Dietary Supplement: Orange JuiceCoingestion of 240 ml of orange juice with 10 mg of montelukast. |
| 3 | Placebo comparator | Dietary Supplement: GatoradeCoingestion of 240 ml of Gatorade with 10 mg of montelukast. |
Who may qualify
- Ages
- 15 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- Doctor diagnosed asthma.
- Must not be taking any medications except for inhaled steroids.
Key exclusion criteria (4 listed)
- Clinical conditions other than asthma.
- Upper respiratory tract infection within the past 30 days.
- Gastrointestinal conditions.
- Unable to stop taking or are required to begin taking any type of oral medication for the duration of the trial
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 |
|---|---|---|
| Grapefruit juiceAlso: Brand: Great Value frozen concentrated grapefruit juice(Walmart).Coingestion of 240 ml of grapefruit juice with 10 mg of montelukast. | Dietary supplement | 1 |
| Orange JuiceAlso: Brand: Winn Dixie orange juice (Winn Dixie).Coingestion of 240 ml of orange juice with 10 mg of montelukast. | Dietary supplement | 2 |
| GatoradeAlso: Brand: Gatorade Rain.Coingestion of 240 ml of Gatorade with 10 mg of montelukast. | Dietary supplement | 3 |
Primary outcome
Area under the concentration vs. time curve for the serum concentration of montelukast when coingested with grapefruit juice, orange juice, or Gatorade.
Time frame: Within 12 hours after administration of a single 10 mg dose.
1 secondary outcome
Improvement in respiratory function as assessed by spirometry, and impulse oscillometry vs. serum concentration of montelukast.
Time frame: Within 12 hours after administration of a single 10 mg dose.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2025.
- Background: PubMed 17397245Lima JJ. Treatment heterogeneity in asthma: genetics of response to leukotriene modifiers. Mol Diagn Ther. 2007;11(2):97-104. doi: 10.1007/BF03256228.
- Background: PubMed 16293801Lima JJ, Zhang S, Grant A, Shao L, Tantisira KG, Allayee H, Wang J, Sylvester J, Holbrook J, Wise R, Weiss ST, Barnes K. Influence of leukotriene pathway polymorphisms on response to montelukast in asthma. Am J Respir Crit Care Med. 2006 Feb 15;173(4):379-85. doi: 10.1164/rccm.200509-1412OC. Epub 2005 Nov 17.
- Merck's Singulair siteLink provided by the sponsor.
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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.
Edward B Mougey, Ph.D. principal investigator
Nemours Children's Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Grapefruit juice, Orange Juice and Gatorade in people with Asthma, run by Nemours Children's Clinic at 1 site 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 2 inclusion and 4 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 10 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Area under the concentration vs. time curve for the serum concentration of montelukast when coingested with grapefruit juice, orange juice, or Gatorade. (time frame: Within 12 hours after administration of a single 10 mg dose.). 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 NCT00513760, which also lists 2 linked publications.
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 10 Feb 2025.