Congestive Heart FailurePhase 1/2ACETO-TCANCT01787851
Study of the Acute Effects of Triheptanoin in Heart Failure
A Phase 1/2 study testing Triheptanoin oil in people with Congestive Heart Failure and Non-ischemic Cardiomyopathy, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial summary
Patients with dilated cardiomyopathy who present for indwelling right heart catheterization will be enrolled and randomized to either control or triheptanoin oil for five days. Hemodynamics will be assess serially. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Congestive Heart Failure, Non-ischemic Cardiomyopathy
- What is being tested?
- Triheptanoin oil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2013to Feb 2014
- Phase
- Phase 1/2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients will be eligible for inclusion in this protocol if they satisfy the following criteria:
- DCM with left ventricular ejection fraction (LVEF) ≤40%
- New York Heart Association (NYHA) class III-IV symptoms
- age ≥18
- an indwelling PA catheter
- and an anticipated clinical requirement for a PA catheter for at least five days.
Who cannot join
- Patients will be ineligible for inclusion in this protocol if they have any of the following:
- urgent (<6 hr) need for (or increase in) inotropic support (INTERMACS profile 1)
- diabetes mellitus
- known disorder of the respiratory chain or mitochondrial cardiomyopathy
- significant hyperlipidemia with triglyceride value >300mg/dL
- normal cardiac index (>2.5L/min/m2) on initial right heart catheterization
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- indwelling intra-aortic balloon pump
- chronic liver disease
- severe renal dysfunction (CKD stage IV-V) with creatinine clearance <30 mL/min/1.73m2
- more than moderate valvular stenosis or regurgitation
- pregnancy or breastfeeding
- peripartum cardiomyopathy diagnosed within the past year
- inability to provide informed consent
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas-Southwestern
Dallas, Texas, 75390
About this study
Official title: Assessment of the Clinical Effects of Triheptanoin Oil to Target Cardiac Anaplerosis in Congestive Heart Failure- Acute Study
Patients with dilated cardiomyopathy who present for indwelling right heart catheterization will be enrolled and randomized to either control or triheptanoin oil for five days. Hemodynamics will be assess serially.
Read the detailed description
Consecutive patients with DCM presenting for a right heart catheterization will be enrolled. All patients will be presenting electively for hemodynamic assessment and will have their PA catheter left in place after their catheterization as part of their usual care. Post-procedure, patients will be monitored in the coronary care unit, which is routine for patients with these catheters. Patients will be approached for potential enrollment in the study protocol. The goal enrollment for this phase of the protocol is 24 patients (12 participants receiving triheptanoin and 10 receiving placebo).
Patients will randomly be assigned to receive either triheptanoin oil or control treatment (sugar syrup) four times a day one hour before meals and at night for five days. All patients will be given a low fat, low simple sugar diet to avoid potential substrate competition from high serum levels of fats and glucose for the duration of the study procedure. Participants will be blinded to their treatment assignment.
Treatment arm: The standard dose of triheptanoin oil for adults is 1-2gm/kg/24 hours. For purposes of this study, we will administer 0.25mg/kg four-times per day. The liquid study drug will be mixed into sugar-free, low fat yogurt, pudding or nutritional supplement shake, depending on patient preference.
Control arm: One tablespoon of sugar syrup will be mixed into sugar-free, low fat yogurt, pudding or nutritional supplement shake four-times per day before meals.
Thermodilution cardiac index and PCWP will be measured from the indwelling PA catheter at baseline and hourly for the first six hours. During this time, initiation or upward titration of vasodilator and inotropic mediations will be discouraged although the medications will be continued in patients previously on these medications. Patients requiring such vasoactive medications on an urgent basis will have been excluded from study participation (see below). After the first six hours, measurements will be recorded once a day, 90 minutes following ingestion of study medication for the four days of treatment, as well as for the following day off study medication (in order to assess off-treatment hemodynamics). Number and dose of intravenous vasoactive medications will be recorded daily.
The main outcome of interest is the change in cardiac index over the first 6 hours of the study period (before initiation of any other vasoactive medications). Pre-and post-cardiac index will be compared with a paired t-test. With 10 patients per study group, we have 80% power to detect a clinically significant 20% difference (0.4L/min/m2) in cardiac index between treatment assignments. Assuming the need for a non-parametric analysis a "standard" 20% increase in sample size will need sought.
Additionally, the change in cardiac output and PCWP over the five day study period will be compared between group assignments (control vs. triheptanoin oil). Either Friedman's test or ANOVA for repeated measures (depending on satisfaction of the normality assumption) will be employed to detect serial changes between each treatment. Between-group differences at each time-point will be assessed by a two-sample t-test or the Wilcoxon signed rank test. We will also measure off-treatment effects by comparing day 4 (final treatment day) cardiac output and PCWP with day 6 (one day off treatment).
Five (5) cc of blood will be collected into EDTA tubes from the PA catheter at baseline and hourly for the first six hours of the study. An additional 5cc of blood will be obtained on day 4 and day 5. Serum will be isolated and stored at -80C until completion of the study. At that time, the samples will be assayed for metabolic profiles, to include acylcarnitine and fatty acid metabolites. Prior work has demonstrated significant increases in serum odd-chain fatty acids, acyl-carnitines and ketones following ingestion.These data will inform on the pharmacodynamics of triheptanoin metabolism in the setting of HF. At baseline and on day 4 a urine sample will be obtained and assayed for species related to proprionate metabolism.
- Being tested
- Triheptanoin oil
- Keywords
- Heart failure, Anaplerosis, Medium-chain fatty acid
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Triheptanoin oilDrug
| Study group | Role | What they receive |
|---|---|---|
| Triheptanoin oil | Active comparator | The standard dose of triheptanoin oil for adults is 1-2gm/kg/24 hours. For purposes of this study, we will administer 0.25mg/kg four-times per day. The liquid study drug will be mixed into sugar-free, low fat yogurt, pudding or nutritional supplement shake, depending on patient preference. Receives: Drug: Triheptanoin oil |
| Simple sugar | Placebo comparator | 0.25mg/kg of sugar syrup will be mixed into sugar-free, low fat yogurt, pudding or nutritional supplement shake four-times per day before meals. Receives: Drug: Triheptanoin oil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cardiac output/index
The main outcome of interest is the change in cardiac index over the first 6 hours of the study period (before initiation of any other vasoactive medications). Pre-and post-cardiac index will be compared with a paired t-test. With 10 patients per study group, we have 80% power to detect a clinically significant 20% difference (0.4L/min/m2) in cardiac index between treatment assignments. Assuming the need for a non-parametric analysis a "standard" 20% increase in sample size will need sought. This yields a final 12 patient per group (n=24 total) sample size
Measured: 6 hours
Secondary outcomes (1)
Cardiac Output/index and pulmonary capillary wedge pressure
Measured: 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2013 (estimated)
- Study startFeb 2013
- Primary completionFeb 2014
- Study completionFeb 2014
Why it stopped: eIRB closed, no patient enrolled
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Congestive Heart FailureStudies of the same condition, open and under way.
- More trials run by University of Texas Southwestern 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Aslan Turer, University of Texas Southwestern Medical Center
- Investigators
- Aslan T Turer, MD, MHS, Principal investigator, UT-Southwestern
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01787851
- Sponsor's protocol ID
- UTSW 65827-1
- Acronym
- ACETO-TCA
- Status last verified
- Dec 2018
- First submitted
- 6 Feb 2013
- Last updated
- 14 Dec 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of the Clinical Effects of Triheptanoin Oil to Target Cardiac Anaplerosis in Congestive Heart Failure- Acute Study
- ClinicalTrials.gov ID
- NCT01787851
- Acronym / sponsor ID
- ACETO-TCA / UTSW 65827-1
- Keywords
- Heart failure, Anaplerosis, Medium-chain fatty acid
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: eIRB closed, no patient enrolled
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Study start
- Feb 2013 (actual)
- Primary completion
- Feb 2014 (actual)
- Study completion
- Feb 2014 (actual)
- First posted
- 11 Feb 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.
Patients with dilated cardiomyopathy who present for indwelling right heart catheterization will be enrolled and randomized to either control or triheptanoin oil for five days. Hemodynamics will be assess serially.
Detailed description
Consecutive patients with DCM presenting for a right heart catheterization will be enrolled. All patients will be presenting electively for hemodynamic assessment and will have their PA catheter left in place after their catheterization as part of their usual care. Post-procedure, patients will be monitored in the coronary care unit, which is routine for patients with these catheters. Patients will be approached for potential enrollment in the study protocol. The goal enrollment for this phase of the protocol is 24 patients (12 participants receiving triheptanoin and 10 receiving placebo).
Patients will randomly be assigned to receive either triheptanoin oil or control treatment (sugar syrup) four times a day one hour before meals and at night for five days. All patients will be given a low fat, low simple sugar diet to avoid potential substrate competition from high serum levels of fats and glucose for the duration of the study procedure. Participants will be blinded to their treatment assignment.
Treatment arm: The standard dose of triheptanoin oil for adults is 1-2gm/kg/24 hours. For purposes of this study, we will administer 0.25mg/kg four-times per day. The liquid study drug will be mixed into sugar-free, low fat yogurt, pudding or nutritional supplement shake, depending on patient preference.
Control arm: One tablespoon of sugar syrup will be mixed into sugar-free, low fat yogurt, pudding or nutritional supplement shake four-times per day before meals.
Thermodilution cardiac index and PCWP will be measured from the indwelling PA catheter at baseline and hourly for the first six hours. During this time, initiation or upward titration of vasodilator and inotropic mediations will be discouraged although the medications will be continued in patients previously on these medications. Patients requiring such vasoactive medications on an urgent basis will have been excluded from study participation (see below). After the first six hours, measurements will be recorded once a day, 90 minutes following ingestion of study medication for the four days of treatment, as well as for the following day off study medication (in order to assess off-treatment hemodynamics). Number and dose of intravenous vasoactive medications will be recorded daily.
The main outcome of interest is the change in cardiac index over the first 6 hours of the study period (before initiation of any other vasoactive medications). Pre-and post-cardiac index will be compared with a paired t-test. With 10 patients per study group, we have 80% power to detect a clinically significant 20% difference (0.4L/min/m2) in cardiac index between treatment assignments. Assuming the need for a non-parametric analysis a "standard" 20% increase in sample size will need sought.
Additionally, the change in cardiac output and PCWP over the five day study period will be compared between group assignments (control vs. triheptanoin oil). Either Friedman's test or ANOVA for repeated measures (depending on satisfaction of the normality assumption) will be employed to detect serial changes between each treatment. Between-group differences at each time-point will be assessed by a two-sample t-test or the Wilcoxon signed rank test. We will also measure off-treatment effects by comparing day 4 (final treatment day) cardiac output and PCWP with day 6 (one day off treatment).
Five (5) cc of blood will be collected into EDTA tubes from the PA catheter at baseline and hourly for the first six hours of the study. An additional 5cc of blood will be obtained on day 4 and day 5. Serum will be isolated and stored at -80C until completion of the study. At that time, the samples will be assayed for metabolic profiles, to include acylcarnitine and fatty acid metabolites. Prior work has demonstrated significant increases in serum odd-chain fatty acids, acyl-carnitines and ketones following ingestion.These data will inform on the pharmacodynamics of triheptanoin metabolism in the setting of HF. At baseline and on day 4 a urine sample will be obtained and assayed for species related to proprionate metabolism.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Triheptanoin oil | Active comparator | Drug: Triheptanoin oilThe standard dose of triheptanoin oil for adults is 1-2gm/kg/24 hours. For purposes of this study, we will administer 0.25mg/kg four-times per day. The liquid study drug will be mixed into sugar-free, low fat yogurt, pudding or nutritional supplement shake, depending on patient preference. |
| Simple sugar | Placebo comparator | Drug: Triheptanoin oil0.25mg/kg of sugar syrup will be mixed into sugar-free, low fat yogurt, pudding or nutritional supplement shake four-times per day before meals. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients will be eligible for inclusion in this protocol if they satisfy the following criteria:
- DCM with left ventricular ejection fraction (LVEF) ≤40%
- New York Heart Association (NYHA) class III-IV symptoms
- age ≥18
- an indwelling PA catheter
Key exclusion criteria (13 listed)
- Patients will be ineligible for inclusion in this protocol if they have any of the following:
- urgent (<6 hr) need for (or increase in) inotropic support (INTERMACS profile 1)
- diabetes mellitus
- known disorder of the respiratory chain or mitochondrial cardiomyopathy
- significant hyperlipidemia with triglyceride value >300mg/dL
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 |
|---|---|---|
| Triheptanoin oil | Drug | Simple sugar, Triheptanoin oil |
Primary outcome
Cardiac output/index
Time frame: 6 hours
The main outcome of interest is the change in cardiac index over the first 6 hours of the study period (before initiation of any other vasoactive medications). Pre-and post-cardiac index will be compared with a paired t-test. With 10 patients per study group, we have 80% power to detect a clinically significant 20% difference (0.4L/min/m2) in cardiac index between treatment assignments. Assuming the need for a non-parametric analysis a "standard" 20% increase in sample size will need sought. This yields a final 12 patient per group (n=24 total) sample size
1 secondary outcome
Cardiac Output/index and pulmonary capillary wedge pressure
Time frame: 5 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Dec 2018.
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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.
Aslan T Turer, MD, MHS principal investigator
UT-Southwestern
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Triheptanoin oil in people with Congestive Heart Failure and Non-ischemic Cardiomyopathy, run by University of Texas Southwestern Medical Center 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 6 inclusion and 13 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: withdrawn, as of the sponsor's last update on 14 Dec 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. 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 combined 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.
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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Cardiac output/index (time frame: 6 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 Dec 2018.