Congestive Heart FailurePhase 1NCT01440335
Initial Study of Fenoterol as a Treatment for Heart Failure
A Phase 1 study testing Oral R,R'-Fenoterol and Oral Racemic Fenoterol in people with Congestive Heart Failure, run by National Institute on Aging (NIA) at 1 site in United States.
Trial summary
Background: Fenoterol has been used to treat asthma by opening up the airways in the lungs. It also increases the heart rate without significantly increasing blood pressure. This means that it may help improve heart function by boosting the heart's output. Read more about this study
- Who is it for?
- Ages 21 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Congestive Heart Failure
- What is being tested?
- Oral R,R'-Fenoterol and Oral Racemic Fenoterol
- Type of treatment
- Pill or oral medicine
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Jul 2011to 15 Apr 2014
- Phase
- Phase 1
- 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 21 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
None listed.
Who cannot join
- Resting sitting blood pressure greater than 140/90 mm Hg, resting heart rate greater than 100 bpm
- Abnormal laboratory examination (ALT and AST greater than 1.5 times the normal range, other labs within 10% of normal range); abnormal troponin screening level will be an exclusion.
- Clinically significant abnormality on EKG (major Q waves, evidence of heart block, significant conduction disease, QT prolongation)
- Clinically significant abnormality on Echocardiogram (ejection fraction less than 50 percent, valvular heart disease of moderate severity, pulmonary hypertension with PASP greater than 40mm Hg)
- Evidence of illicit drug use or alcohol abuse
- History of Human Immunodeficiency Virus (HIV) infection
Show all 19Show fewer
- History of active or chronic Hepatitis B and/or C infection
- History of malignancy (other than non-invasive skin cancer)
- History of coronary disease, conduction system disease, pacemaker, atrial fibrillation/flutter, ventricular tachycardia/fibrillation, significant valvular disease, or other cardiovascular disease
- History of asthma -- reactive airway disease
- History of seizures or other neurologic diseases
- History of liver or renal diseases
- History of gastrointestinal or endocrine disorders (other than mild dyspepsia)
- Medication use other than occasional use of over-the-counter drugs and/or contraceptives
- Any medication or herbal drug use within the past 3 days before study participation other than contraceptives
- Any medical history that, in the opinion of the investigator(s), will make participation of the subject in the study unsafe
- Participation in another clinical trial involving any pharmacologic agents or blood loss within the past 30 days
- Donation of blood or blood products within the past 56 days
- Women who are of childbearing potential and not using acceptable forms of contraception will be excluded.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Aging, Clinical Research Unit
Baltimore, Maryland, 21224
About this study
Official title: A Study of (R, R') and (S,S': R,R')- Fenoterol: Initial Clinical Evaluation for Pharmacokinetics, Pharmacodynamics, and Safety
Background:
- Fenoterol has been used to treat asthma by opening up the airways in the lungs. It also increases the heart rate without significantly increasing blood pressure. This means that it may help improve heart function by boosting the heart's output. Researchers have developed a different form of the drug that may be given to individuals with heart trouble. This new form needs more testing. It is especially important to compare the new form with the original form of the drug used to treat asthma.
Read more
Objectives:
- To compare how safe and effective two different forms of Fenoterol are in improving heart function.
Eligibility:
- Healthy people between 21 and 60 years of age who have no history of heart disease.
Design:
- People will be screened with a medical history, physical exam, blood and urine tests, and heart function studies.
- Those in the study will have two 36-hour inpatient study visits. At each visit, they will have a physical exam and blood and urine tests. They will fast overnight and then receive one of the two forms of Fenoterol first thing in the morning. They will not know whether they are getting the original or the modified form of the drug. After receiving the drug, they will provide frequent blood and urine samples for 24 hours. They will have a final exam before being discharged.
- Those who take part in the study will have a followup visit 5 to 7 days after the end of each study visit. They will provide more blood and urine samples and have a physical exam.
Read the detailed description
Fenoterol is a drug that has been used for the treatment of disease like asthma for many years. It is available in Canada in an inhaled form where it is called Berotec . Fenoterol stimulates receptors in the body called Beta Adrenergic Receptors and is therefore in a family of drugs called Beta Agonists. While one particular form of the drug, called a Racemic mixture has traditionally been used for asthma, multiple forms of the drug have now been produced and it is possible that using one of the newer forms of the drug will have benefits for people with heart failure.
Treatment for heart failure is a complex problem. It is a problem of the heart not pumping enough blood to meet the demands of the body and a number of changes that ultimately prove harmful in an attempt to compensate for this failure. Scientists have observed several effects of Fenoterol that may prove beneficial to people with heart failure. Use of the older Fenoterol (Racemic) mixture indicates that the drug causes the heart to pump more blood out to the rest of the body by increasing a person s heart rate but having little to no effect on their blood pressure. These effects provide a rationale for attempting to develop Fenoterol as a possible treatment for congestive heart failure. It is hoped that this new form of the drug will prove to have even more benefits.
However, the new form of the drug (called the R R form ) has not yet been tested in humans. Animal studies and scientific understanding of these types of mixtures suggest that it will little to no difference between it and the older Racemic form. To test this thinking and determine what doses should be used in future studies, we will conduct a Phase I, escalating dose study in healthy volunteers using the orally administered forms of the older Racemic mixture and newer R R form .
This study will consist of three groups of 6 people taking doses of the drug by mouth and then monitoring their heart rate, blood pressure, blood chemistry, genetic factors, and heart function. The first group will get a 2.5 mg dose of the R R form of the drug on one visit and then a 5 mg dose of the racemic mixture on the other visit. The second group will get a 5mg dose of the R R form on one of their visits and a 10mg dose of the Racemic mixture on the other. Finally, the third group will get a 10mg dose of the R R form on one visit and a 20mg dose of the Racemic mixture on the other. Also, blood will be collected at regular intervals to monitor levels of the drug, its rate of breakdown, changes in blood chemistry, and the testing of various genes. All research will be performed at the National Institute on Aging (NIA) Clinical Research Unit located on the 5th floor of Harbor Hospital in Baltimore, MD.
Testing the safety and breakdown of this drug and comparing it to the older Racemic form will be an important first step in its development as a new drug for heart failure.
The specific aims are:
- A Phase 1 study in healthy volunteers to establish the body s absorption and breakdown of this new form of Fenoterol (R R form) in comparison with the older, established Racemic mixture.
- To monitor the effects of the drug on heart rate, blood pressure, and cardiac structure and function after a person takes the drug.
Endpoint: This study will provide a safety assessment and will determine the pharmacokinetics and bioavailability of (R,R )- and racemic Fenoterol in healthy subjects. In addition, information will be gained about the pharmacodynamics of Fenoterol. This will provide information for future studies that will evaluate (R,R )-Fenoterol as a potential treatment for congestive heart failure.
- Conditions
- Congestive Heart Failure
- Being tested
- Oral R,R'-Fenoterol, Oral Racemic Fenoterol
- Keywords
- Fenoterol, Pharmacodynamics, Pharmacokinetics, Safety, Beta Adrenergic Agonist
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral R,R'-FenoterolDrug
Oral Racemic FenoterolDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety assessment
Pharmacokinetics
Bioavailability
Secondary outcomes (4)
Pharmacodynamic effects of heart rate
Blood Pressure
Echocardiographic indices of cardiac structure and function
B2-AR lymphocyte binding and function during drug exposure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2011 (estimated)
- Study start10 Jul 2011
- Primary completion15 Apr 2014
- Study completion15 Apr 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Congestive Heart FailureStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute on Aging (NIA)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- James B Strait, M.D., Principal investigator, National Institute on Aging (NIA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01440335
- Sponsor's protocol ID
- 999911153
- Other IDs
- 11-AG-N153
- Status last verified
- 7 Jan 2015
- First submitted
- 23 Sep 2011
- Last updated
- 5 Jul 2018
- Results posted
- No
Publications
Wilson AA, Wang J, Koch P, Walle T. Stereoselective sulphate conjugation of fenoterol by human phenolsulphotransferases. Xenobiotica. 1997 Nov;27(11):1147-54. doi: 10.1080/004982597239903.
PubMed 9413918Ahmet I, Krawczyk M, Heller P, Moon C, Lakatta EG, Talan MI. Beneficial effects of chronic pharmacological manipulation of beta-adrenoreceptor subtype signaling in rodent dilated ischemic cardiomyopathy. Circulation. 2004 Aug 31;110(9):1083-90. doi: 10.1161/01.CIR.0000139844.15045.F9. Epub 2004 Aug 16.
PubMed 15313944Anderson G, Wilkins E, Jariwalla AG. Fenoterol in asthma. Br J Dis Chest. 1979 Jan;73(1):81-4.
PubMed 373786
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of (R, R') and (S,S': R,R')- Fenoterol: Initial Clinical Evaluation for Pharmacokinetics, Pharmacodynamics, and Safety
- ClinicalTrials.gov ID
- NCT01440335
- Acronym / sponsor ID
- 999911153
- Conditions
- Congestive Heart Failure
- Keywords
- Fenoterol, Pharmacodynamics, Pharmacokinetics, Safety, Beta Adrenergic Agonist
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- National Institute on Aging (NIA)US National Institutes of Health
- Study start
- 10 Jul 2011
- Primary completion
- 15 Apr 2014 (actual)
- Study completion
- 15 Apr 2014 (actual)
- First posted
- 26 Sep 2011 (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.
Background:
- Fenoterol has been used to treat asthma by opening up the airways in the lungs. It also increases the heart rate without significantly increasing blood pressure. This means that it may help improve heart function by boosting the heart's output. Researchers have developed a different form of the drug that may be given to individuals with heart trouble. This new form needs more testing. It is especially important to compare the new form with the original form of the drug used to treat asthma.
Objectives:
- To compare how safe and effective two different forms of Fenoterol are in improving heart function.
Eligibility:
- Healthy people between 21 and 60 years of age who have no history of heart disease.
Design:
- People will be screened with a medical history, physical exam, blood and urine tests, and heart function studies.
- Those in the study will have two 36-hour inpatient study visits. At each visit, they will have a physical exam and blood and urine tests. They will fast overnight and then receive one of the two forms of Fenoterol first thing in the morning. They will not know whether they are getting the original or the modified form of the drug. After receiving the drug, they will provide frequent blood and urine samples for 24 hours. They will have a final exam before being discharged.
- Those who take part in the study will have a followup visit 5 to 7 days after the end of each study visit. They will provide more blood and urine samples and have a physical exam.
Detailed description
Fenoterol is a drug that has been used for the treatment of disease like asthma for many years. It is available in Canada in an inhaled form where it is called Berotec . Fenoterol stimulates receptors in the body called Beta Adrenergic Receptors and is therefore in a family of drugs called Beta Agonists. While one particular form of the drug, called a Racemic mixture has traditionally been used for asthma, multiple forms of the drug have now been produced and it is possible that using one of the newer forms of the drug will have benefits for people with heart failure.
Treatment for heart failure is a complex problem. It is a problem of the heart not pumping enough blood to meet the demands of the body and a number of changes that ultimately prove harmful in an attempt to compensate for this failure. Scientists have observed several effects of Fenoterol that may prove beneficial to people with heart failure. Use of the older Fenoterol (Racemic) mixture indicates that the drug causes the heart to pump more blood out to the rest of the body by increasing a person s heart rate but having little to no effect on their blood pressure. These effects provide a rationale for attempting to develop Fenoterol as a possible treatment for congestive heart failure. It is hoped that this new form of the drug will prove to have even more benefits.
However, the new form of the drug (called the R R form ) has not yet been tested in humans. Animal studies and scientific understanding of these types of mixtures suggest that it will little to no difference between it and the older Racemic form. To test this thinking and determine what doses should be used in future studies, we will conduct a Phase I, escalating dose study in healthy volunteers using the orally administered forms of the older Racemic mixture and newer R R form .
This study will consist of three groups of 6 people taking doses of the drug by mouth and then monitoring their heart rate, blood pressure, blood chemistry, genetic factors, and heart function. The first group will get a 2.5 mg dose of the R R form of the drug on one visit and then a 5 mg dose of the racemic mixture on the other visit. The second group will get a 5mg dose of the R R form on one of their visits and a 10mg dose of the Racemic mixture on the other. Finally, the third group will get a 10mg dose of the R R form on one visit and a 20mg dose of the Racemic mixture on the other. Also, blood will be collected at regular intervals to monitor levels of the drug, its rate of breakdown, changes in blood chemistry, and the testing of various genes. All research will be performed at the National Institute on Aging (NIA) Clinical Research Unit located on the 5th floor of Harbor Hospital in Baltimore, MD.
Testing the safety and breakdown of this drug and comparing it to the older Racemic form will be an important first step in its development as a new drug for heart failure.
The specific aims are:
- A Phase 1 study in healthy volunteers to establish the body s absorption and breakdown of this new form of Fenoterol (R R form) in comparison with the older, established Racemic mixture.
- To monitor the effects of the drug on heart rate, blood pressure, and cardiac structure and function after a person takes the drug.
Endpoint: This study will provide a safety assessment and will determine the pharmacokinetics and bioavailability of (R,R )- and racemic Fenoterol in healthy subjects. In addition, information will be gained about the pharmacodynamics of Fenoterol. This will provide information for future studies that will evaluate (R,R )-Fenoterol as a potential treatment for congestive heart failure.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
Who may qualify
- Ages
- 21 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (0 listed)
Key exclusion criteria (19 listed)
- Resting sitting blood pressure greater than 140/90 mm Hg, resting heart rate greater than 100 bpm
- Abnormal laboratory examination (ALT and AST greater than 1.5 times the normal range, other labs within 10% of normal range); abnormal troponin screening level will be an exclusion.
- Clinically significant abnormality on EKG (major Q waves, evidence of heart block, significant conduction disease, QT prolongation)
- Clinically significant abnormality on Echocardiogram (ejection fraction less than 50 percent, valvular heart disease of moderate severity, pulmonary hypertension with PASP greater than 40mm Hg)
- Evidence of illicit drug use or alcohol abuse
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 |
|---|---|---|
| Oral R,R'-Fenoterol | Drug | – |
| Oral Racemic Fenoterol | Drug | – |
Primary outcome
Safety assessment
Pharmacokinetics
Bioavailability
4 secondary outcomes
Pharmacodynamic effects of heart rate
Blood Pressure
Echocardiographic indices of cardiac structure and function
B2-AR lymphocyte binding and function during drug exposure
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 5 Jul 2018.
- Background: PubMed 9413918Wilson AA, Wang J, Koch P, Walle T. Stereoselective sulphate conjugation of fenoterol by human phenolsulphotransferases. Xenobiotica. 1997 Nov;27(11):1147-54. doi: 10.1080/004982597239903.
- Background: PubMed 15313944Ahmet I, Krawczyk M, Heller P, Moon C, Lakatta EG, Talan MI. Beneficial effects of chronic pharmacological manipulation of beta-adrenoreceptor subtype signaling in rodent dilated ischemic cardiomyopathy. Circulation. 2004 Aug 31;110(9):1083-90. doi: 10.1161/01.CIR.0000139844.15045.F9. Epub 2004 Aug 16.
- Background: PubMed 373786Anderson G, Wilkins E, Jariwalla AG. Fenoterol in asthma. Br J Dis Chest. 1979 Jan;73(1):81-4.
Related trials for Congestive Heart Failure
RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life(COREVIVE-HFrEF)
Heart Failure With Reduced Ejection Fraction, Iron Deficiency
Not yet recruitingPhase 2
A Study of Bimagrumab in Participants With HFpEF
Heart Failure, Diastolic, Diastolic Heart Failure
Recruiting
Evaluation of a French Hospital Discharge Therapeutic Education Program by Nurses for Heart Failure Patient (EduSor)
Heart Failure
Active, not recruiting
Assessment of Combined CCM and ICD Device in HFrEF
Heart Failure, Heart Failure With Reduced Ejection Fraction
Not yet recruiting
RELIEVE-HFrEF TRIAL: REducing Lung congestIon Symptoms Using the v-wavE Shunt in adVancEd Heart Failure With Reduced EF
Heart Failure and Reduced Ejection Fraction, Heart Failure Chronic
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.
James B Strait, M.D. principal investigator
National Institute on Aging (NIA)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Oral R,R'-Fenoterol and Oral Racemic Fenoterol in people with Congestive Heart Failure, run by National Institute on Aging (NIA) 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 0 inclusion and 19 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 5 Jul 2018. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Safety assessment. The study lists 3 primary outcomes in all. 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 NCT01440335, which also lists 3 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 5 Jul 2018.