Diastolic Heart FailureNCT01778894
Mathematical Modeling to Determine Basic Muscle Properties in the Failing Heart
An observational study of Diastolic Heart Failure, run by University of Nebraska at 1 site in United States.
Trial summary
According to the most recent information released by the American Heart Association, heart failure affects 5.8 million Americans and over 23 million people worldwide. In particular, diastolic heart failure (DHF) has emerged in approximately half of those suffering from heart disease and has become a major public… Read more about this study
- Who is it for?
- Ages 19 years and olderHealthy volunteers can take part
- Conditions the study is for
- Diastolic Heart Failure
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2013to 3 Feb 2022
- Phase
- Observational
- 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 19 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Normal controls will be recruited from the Omaha community. Subjects with Diastolic Heart Dysfunction and/or Failure will be selected from The University of Nebraska Medical Center Heart Clinic or from The Nebraska Medical Center Hospital.
Who may be able to join
- Subjects must be 19 years of age or older
- Control subjects must have no prior history or current signs of heart disease.
- Subjects with heart failure must meet one or more of the following criteria:
- Documented Diastolic Heart Failure, Grade II or greater (via NYHA functional class)
- Grade II or greater Diastolic Dysfunction by echocardiographic evaluation
Who cannot join
- Subjects under the age of 19 or unable to give consent will be excluded from this study.
- Greater than mild valvular disease
- Prior valve repair/replacement
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Nebraska Medical Center
Omaha, Nebraska, 68198
About this study
According to the most recent information released by the American Heart Association, heart failure affects 5.8 million Americans and over 23 million people worldwide. In particular, diastolic heart failure (DHF) has emerged in approximately half of those suffering from heart disease and has become a major public health problem for many reasons, including the complexity of the disease, lack of effective drugs/therapies, requirement of invasive tests to diagnose and monitor DHF, and the absence of a suitable scientific model to study the disease. Scientists and physicians alike still do not fully understand what happens to the muscles in the heart (myocardium) patients who present with diastolic dysfunction or DHF. Therefore, the medical field is in need of an accurate model that can evaluate how diastolic dysfunction leads to heart failure and what happens at a cellular level as this disease emerges and progresses.
Read the detailed description
Our group has developed a mathematical model of the heart that gathers data from a procedure called an echocardiograph (echo) to analyze how muscles in the heart are functioning. This model incorporates how the heart muscle functions on a cellular level along with the overall functionality of the heart.
We hypothesize that this model will measure the specific properties of the heart muscle that affect their ability to contract and relax. This study will determine whether these properties will be different in patients with DHF compared to healthy controls. We also propose that these abnormalities in the heart muscle will correlate with the patient's degree of heart failure and their prognosis when doctors evaluate using standard clinical tests.
This study will be conducted at the University of Nebraska Medical Center (UNMC). 40 subjects will be enrolled, 20 healthy controls with no history of heart disease and 20 subjects who have been diagnosed with diastolic heart failure. Healthy controls will be required to undergo 1 echocardiograph procedure at UNMC. Subjects diagnosed with DHF will be required to undergo 6 echocardiograph procedure over the course of 2 years.
- Conditions
- Diastolic Heart Failure
- Keywords
- Diastolic Dysfunction, Diastolic Heart Failure, Diastolic, Echocardiography
- Medical subject headings
- Heart Failure, Diastolic, Heart Murmurs
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Healthy Control | Healthy controls with no history of heart disease or heart failure. Subjects will undergo a medical history review and 1 echocardiograph procedure. | |
| >Grade 2 Diastolic Dysfunction | Diastolic Heart Failure, > Grade II (NYHA functional class) and/or > Grade II Diastolic Dysfunction as evaluated by echocardiography |
What is being measured
The primary outcome is the main question the study is designed to answer.
The longitudinal assessment of myocardial properties in subjects with Diastolic Heart Failure.
Our mathematical model of the heart integrates the cellular mechanisms of sarcomere dynamics with the overall functional properties of the ventricle. Utilizing specific measurements captured by echo, estimates of basic muscle properties in subjects suffering from DHF will be compared to observed properties. Echo measurements will be taken at baseline and 2 weeks, 4 months, 8 months, 1 year, and 2 years following therapy.
Measured: 2 years
Secondary outcomes (2)
Correlation of observed muscle properties to clinical outcomes/status.
Clinical outcome measurements, including hospitalizations, New York Heart Association (NYHA) class, and mortality, will be collected to determine effectiveness of current therapy for diastolic heart failure. By tracking patient outcomes and measured clinical endpoints, the degree of material parameter abnormality affecting clinical outcomes of subjects will be tested using multivariate regression with the material parameters derived from the model. The dependent variables and covariates such as age, sex, ejection fraction, presence of co-morbidities such as coronary artery disease, diabetes, and hypertension will also be included in the analysis.
Measured: 2 years
Validation of the developing mathematical model using the data points collected from echocardiographic procedures
An optimization driver program that controls the parameter estimation has been developed and will be validated. To estimate unknown material parameters, multiple forward model simulations are obtained to estimate the partial derivatives of the least squares objective function with respect to the material parameters. Best-fit parameters will be determined for each DHF patient and each control using cylindrical, spherical and ellipsoidal models. Each of these parameters represents a unique aspect of sarcomere and ventricular matrix constitutive behavior. Best-fit material parameters for each patient will be compared with those obtained from the control groups.
Measured: 1 baseline echocardiograph
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2013 (estimated)
- Study start1 Sep 2013
- Primary completion3 Feb 2022
- Study completion3 Feb 2022
Why it stopped: Administratively closed because no Continuing Review submitted
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 Diastolic 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Moulton J Moulton, MD, Principal investigator, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01778894
- Sponsor's protocol ID
- 0623-12-EP
- Status last verified
- Aug 2023
- First submitted
- 25 Jan 2013
- Last updated
- 29 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kass DA, Bronzwaer JG, Paulus WJ. What mechanisms underlie diastolic dysfunction in heart failure? Circ Res. 2004 Jun 25;94(12):1533-42. doi: 10.1161/01.RES.0000129254.25507.d6.
PubMed 15217918Paulus WJ, Tschope C, Sanderson JE, Rusconi C, Flachskampf FA, Rademakers FE, Marino P, Smiseth OA, De Keulenaer G, Leite-Moreira AF, Borbely A, Edes I, Handoko ML, Heymans S, Pezzali N, Pieske B, Dickstein K, Fraser AG, Brutsaert DL. How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur Heart J. 2007 Oct;28(20):2539-50. doi: 10.1093/eurheartj/ehm037. Epub 2007 Apr 11.
PubMed 17428822Moulton MJ, Creswell LL, Actis RL, Myers KW, Vannier MW, Szabo BA, Pasque MK. An inverse approach to determining myocardial material properties. J Biomech. 1995 Aug;28(8):935-48. doi: 10.1016/0021-9290(94)00144-s.
PubMed 7673261
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mathematical Modeling to Determine Basic Muscle Properties in the Failing Heart
- ClinicalTrials.gov ID
- NCT01778894
- Acronym / sponsor ID
- 0623-12-EP
- Conditions
- Diastolic Heart Failure
- Keywords
- Diastolic Dysfunction, Diastolic Heart Failure, Diastolic, Echocardiography
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Administratively closed because no Continuing Review submitted
- Enrolment
- 37 participants (actual)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Study start
- 1 Sep 2013 (actual)
- Primary completion
- 3 Feb 2022 (actual)
- Study completion
- 3 Feb 2022 (actual)
- First posted
- 29 Jan 2013 (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.
According to the most recent information released by the American Heart Association, heart failure affects 5.8 million Americans and over 23 million people worldwide. In particular, diastolic heart failure (DHF) has emerged in approximately half of those suffering from heart disease and has become a major public health problem for many reasons, including the complexity of the disease, lack of effective drugs/therapies, requirement of invasive tests to diagnose and monitor DHF, and the absence of a suitable scientific model to study the disease. Scientists and physicians alike still do not fully understand what happens to the muscles in the heart (myocardium) patients who present with diastolic dysfunction or DHF. Therefore, the medical field is in need of an accurate model that can evaluate how diastolic dysfunction leads to heart failure and what happens at a cellular level as this disease emerges and progresses.
Detailed description
Our group has developed a mathematical model of the heart that gathers data from a procedure called an echocardiograph (echo) to analyze how muscles in the heart are functioning. This model incorporates how the heart muscle functions on a cellular level along with the overall functionality of the heart.
We hypothesize that this model will measure the specific properties of the heart muscle that affect their ability to contract and relax. This study will determine whether these properties will be different in patients with DHF compared to healthy controls. We also propose that these abnormalities in the heart muscle will correlate with the patient's degree of heart failure and their prognosis when doctors evaluate using standard clinical tests.
This study will be conducted at the University of Nebraska Medical Center (UNMC). 40 subjects will be enrolled, 20 healthy controls with no history of heart disease and 20 subjects who have been diagnosed with diastolic heart failure. Healthy controls will be required to undergo 1 echocardiograph procedure at UNMC. Subjects diagnosed with DHF will be required to undergo 6 echocardiograph procedure over the course of 2 years.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Healthy Control | – | –Healthy controls with no history of heart disease or heart failure. Subjects will undergo a medical history review and 1 echocardiograph procedure. |
| >Grade 2 Diastolic Dysfunction | – | –Diastolic Heart Failure, > Grade II (NYHA functional class) and/or > Grade II Diastolic Dysfunction as evaluated by echocardiography |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Normal controls will be recruited from the Omaha community. Subjects with Diastolic Heart Dysfunction and/or Failure will be selected from The University of Nebraska Medical Center Heart Clinic or from The Nebraska Medical Center Hospital.
Key inclusion criteria (5 listed)
- Subjects must be 19 years of age or older
- Control subjects must have no prior history or current signs of heart disease.
- Subjects with heart failure must meet one or more of the following criteria:
- Documented Diastolic Heart Failure, Grade II or greater (via NYHA functional class)
- Grade II or greater Diastolic Dysfunction by echocardiographic evaluation
Key exclusion criteria (3 listed)
- Subjects under the age of 19 or unable to give consent will be excluded from this study.
- Greater than mild valvular disease
- Prior valve repair/replacement
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
The longitudinal assessment of myocardial properties in subjects with Diastolic Heart Failure.
Time frame: 2 years
Our mathematical model of the heart integrates the cellular mechanisms of sarcomere dynamics with the overall functional properties of the ventricle. Utilizing specific measurements captured by echo, estimates of basic muscle properties in subjects suffering from DHF will be compared to observed properties. Echo measurements will be taken at baseline and 2 weeks, 4 months, 8 months, 1 year, and 2 years following therapy.
2 secondary outcomes
Correlation of observed muscle properties to clinical outcomes/status.
Time frame: 2 years
Validation of the developing mathematical model using the data points collected from echocardiographic procedures
Time frame: 1 baseline echocardiograph
Results and safety
The study was stopped early (reason given: Administratively closed because no Continuing Review submitted). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2023.
- Background: PubMed 15217918Kass DA, Bronzwaer JG, Paulus WJ. What mechanisms underlie diastolic dysfunction in heart failure? Circ Res. 2004 Jun 25;94(12):1533-42. doi: 10.1161/01.RES.0000129254.25507.d6.
- Background: PubMed 17428822Paulus WJ, Tschope C, Sanderson JE, Rusconi C, Flachskampf FA, Rademakers FE, Marino P, Smiseth OA, De Keulenaer G, Leite-Moreira AF, Borbely A, Edes I, Handoko ML, Heymans S, Pezzali N, Pieske B, Dickstein K, Fraser AG, Brutsaert DL. How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur Heart J. 2007 Oct;28(20):2539-50. doi: 10.1093/eurheartj/ehm037. Epub 2007 Apr 11.
- Background: PubMed 7673261Moulton MJ, Creswell LL, Actis RL, Myers KW, Vannier MW, Szabo BA, Pasque MK. An inverse approach to determining myocardial material properties. J Biomech. 1995 Aug;28(8):935-48. doi: 10.1016/0021-9290(94)00144-s.
- Individual participant dataSharing planned: No
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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.
Moulton J Moulton, MD principal investigator
University of Nebraska
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Diastolic Heart Failure, run by University of Nebraska 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 5 inclusion and 3 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: stopped early, as of the sponsor's last update on 29 Aug 2023. 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.
Are results available for this study?
The study was stopped early (reason given: Administratively closed because no Continuing Review submitted). Results are not available in the source record.
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?
The longitudinal assessment of myocardial properties in subjects with Diastolic Heart Failure. (time frame: 2 years). 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 NCT01778894, 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 29 Aug 2023.