Study of Triheptanoin for Treatment of Long-Chain Fatty Acid Oxidation Disorder
Study Details
Study Description
Brief Summary
Humans eat long-chain fat in their diet and use it for energy during exercise and during periods of fasting. Patients with long-chain fatty acid oxidation disorders cannot use dietary fat for energy. They sometimes develop muscle breakdown, and severe pain with exercise or illness. They can also develop a heart that does not function properly. These patients are tired and expend less energy than people who do not have a long-chain fatty acid oxidation disorder. However, they can use a supplement oil called medium chain triglyceride or MCT. This study will determine if a new experimental oil called Triheptanoin can decrease the muscle pain and increase the heart function and the amount of energy in patients with long-chain fatty acid oxidation disorders. Funding source - FDA's OOPD
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
Recruitment: Patients with a long-chain fatty acid oxidation disorder will be recruited through our clinic, past research participants, a patient support website, and recruitment letters mailed to physicians around the US. We will enroll 16 subjects at OHSU and 16 subjects at the University of Pittsburgh, age 7 to 40, with a disorder in fatty acid oxidation.
Procedures: Subjects will be admitted to the clinical research center for 4 days. They will collect all their urine for 24 hours. Heart function will be measured using ultrasound an electrocardiogram (ECG). The motion of the heart will be measured by magnetic resonance imaging (MRI). For this test, the patient lies in the magnetic field of the MRI machine in the Advanced Imaging Resource Center (AIRC) for about 45 minutes. The amount of muscle and fat in the whole body and inside the liver and muscle will be measured by MRS and by dual X-ray absorptiometry (DEXA). Subjects will walk on a treadmill for about 45 minutes. The amount of Calories they use, their heart rate, and if they burn fat or carbohydrates will be measured. Blood samples will be collected before and after exercise. A meal test will be used to determine how much fat they burn. The subjects will drink a liquid breakfast with a stable isotope labeled fat in the breakfast. Breath and blood samples will be collected before and after the meal. The amount Calories burned by each subject will be measured when they are at rest on a bed by indirect calorimetry. The amount of Calories burned by subjects when they are doing their routine daily activities will be measured at home by doubly labeled water. All of these tests will be done at baseline. Then, subjects will be randomly assigned to consume MCT (current standard of care) or triheptanoin at 20% of their estimated Calorie needs for 4 months. The subject and/or the parent will be taught how to use the supplement oil in their diet for cooking and baking. The subject will be sent home and the oil will be shipped to their home. The study coordinator will call the subject or subject's guardian each week to monitor the subject's diet, potential side effects and assist with diet planning. At the end of 4 months, all of the baseline tests will be repeated.
Triheptanoin is experimental oil. It is a clear, odorless oil that can be mixed with foods and used in cooking. Almost all oils are made from even chains of carbon molecules. Triheptanoin is different because the carbon chains are odd in number. The co-investigator of this study at the University of Pittsburgh, Dr. Jerry Vockely, holds an IND for the prescription, and use of triheptanoin in humans (IND 106011).
Data Analysis: The change in exercise ability, heart function, Calories used and body fat after 4 months will be compared between subjects randomized to MCT versus triheptanoin.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Medium Chain Triglyceride (MCT) Subjects randomized to consume 20% of energy from MCT |
Drug: Triheptanoin
Triglyceride with three heptanoin or 7 carbon fatty acids esterified to a glycerol backbone
Other Names:
|
| Experimental: Triheptanoin Subject randomized to consume 20% of energy from triheptanoin. |
Drug: Triheptanoin
Triglyceride with three heptanoin or 7 carbon fatty acids esterified to a glycerol backbone
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Energy Expenditure [change from baseline after 4 months of treatment]
Total energy expenditure will be measured by doubly labeled water and resting energy expenditure will be measured by indirect calorimetry at baseline and again after 4 months of either MCT or trihpetanoin treatment.
- Ejection Fraction [4 months]
Change in resting ejection fraction over 4 month treatment period
Secondary Outcome Measures
- Exercise Heart Rate [change from baseline to 4 months of treatment]
Subjects will complete a submaximal treadmill exercise study at baseline. Exercise heart heart, ventilation and perceived exertion will be measured. Subjects will be randomized to MCT or triheptanoin supplementation for 4 months. At the end of treatment, the exercise test will be repeated keeping work performed constant. Change in exercise heart rate, ventilation and exertion will be compared between groups.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Confirmed diagnosis of Very long-chain acylCoA dehydrogenase (VLCAD) Deficiency, Carnitine Palmitoyltransferase 2 (CPT2) Deficiency, Mitochondrial Trifunctional Protein (TFP) Deficiency, or Long-chain 3 hydroxyacylCoA dehydrogenase (LCHAD) deficiency
-
7 years
-
Ability to travel to CRC to participate
-
Ability to follow protocol
Exclusion Criteria:
-
Hgb < 10 g/dl
-
Peripheral neuropathy that limits ability to complete treadmill studies
-
Inclusion in another research study that alters macronutrient intake
-
Pregnant females
-
history of myocardial infarction or cardiovascular disease
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Oregon Health & Science University | Portland | Oregon | United States | 97239 |
| 2 | University of Pittsburgh | Pittsburgh | Pennsylvania | United States | 15224 |
Sponsors and Collaborators
- Oregon Health and Science University
- University of Pittsburgh
Investigators
- Principal Investigator: Melanie B Gillingham, PhD, Oregon Health and Science University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- FD003895
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Medium Chain Triglyceride (MCT) | Triheptanoin |
|---|---|---|
| Arm/Group Description | Subjects randomized to consume 20% of energy from MCT Triheptanoin: Triglyceride with three heptanoin or 7 carbon fatty acids esterified to a glycerol backbone | Subject randomized to consume 20% of energy from triheptanoin. Triheptanoin: Triglyceride with three heptanoin or 7 carbon fatty acids esterified to a glycerol backbone |
| Period Title: Overall Study | ||
| STARTED | 16 | 16 |
| COMPLETED | 16 | 16 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Medium Chain Triglyceride (MCT) | Triheptanoin | Total |
|---|---|---|---|
| Arm/Group Description | Subjects randomized to consume 20% of energy from MCT Triheptanoin: Triglyceride with three heptanoin or 7 carbon fatty acids esterified to a glycerol backbone | Subject randomized to consume 20% of energy from triheptanoin. Triheptanoin: Triglyceride with three heptanoin or 7 carbon fatty acids esterified to a glycerol backbone | Total of all reporting groups |
| Overall Participants | 16 | 16 | 32 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
22.3
(12.7)
|
27.2
(15.9)
|
24.8
(14.4)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
10
62.5%
|
10
62.5%
|
20
62.5%
|
| Male |
6
37.5%
|
6
37.5%
|
12
37.5%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
1
6.3%
|
0
0%
|
1
3.1%
|
| Not Hispanic or Latino |
15
93.8%
|
16
100%
|
31
96.9%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
| White |
16
100%
|
16
100%
|
32
100%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
16
100%
|
16
100%
|
32
100%
|
| Body Weight (kilograms) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [kilograms] |
67.1
(26.8)
|
62.1
(23.5)
|
64.6
(24.9)
|
| Ejection Fraction (percent) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [percent] |
63
(5.3)
|
57
(9.2)
|
59.7
(8.0)
|
| Exercise Heart Rate (beats per minute) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [beats per minute] |
132
(7)
|
125
(12)
|
128
(10)
|
| Total Energy Expenditure (kcal/day) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [kcal/day] |
2567
(604)
|
2230
(512)
|
2392
(572)
|
Outcome Measures
| Title | Energy Expenditure |
|---|---|
| Description | Total energy expenditure will be measured by doubly labeled water and resting energy expenditure will be measured by indirect calorimetry at baseline and again after 4 months of either MCT or trihpetanoin treatment. |
| Time Frame | change from baseline after 4 months of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| One subject in each group did not complete the doubly labeled water measures. A total of 15 in each group measured total energy expenditure at baseline and at the end of the study. This value compares the change over treatment. |
| Arm/Group Title | Medium Chain Triglyceride (MCT) | Triheptanoin |
|---|---|---|
| Arm/Group Description | Subjects randomized to consume 20% of energy from MCT Triheptanoin: Triglyceride with three heptanoin or 7 carbon fatty acids esterified to a glycerol backbone | Subject randomized to consume 20% of energy from triheptanoin. Triheptanoin: Triglyceride with three heptanoin or 7 carbon fatty acids esterified to a glycerol backbone |
| Measure Participants | 15 | 15 |
| Mean (Standard Deviation) [kcal/day] |
-73
(335)
|
107
(387)
|
| Title | Ejection Fraction |
|---|---|
| Description | Change in resting ejection fraction over 4 month treatment period |
| Time Frame | 4 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Change in resting ejection fraction over 4 month treatment period calculated as: 4 month ejection fraction-baseline ejection fraction. Only participants with available data are included in this analysis. |
| Arm/Group Title | Medium Chain Triglyceride (MCT) | Triheptanoin |
|---|---|---|
| Arm/Group Description | Subjects randomized to consume 20% of energy from MCT Triheptanoin: Triglyceride with three heptanoin or 7 carbon fatty acids esterified to a glycerol backbone | Subject randomized to consume 20% of energy from triheptanoin. Triheptanoin: Triglyceride with three heptanoin or 7 carbon fatty acids esterified to a glycerol backbone |
| Measure Participants | 11 | 10 |
| Mean (Standard Deviation) [percent] |
-1.91
(4.16)
|
2.14
(4.43)
|
| Title | Exercise Heart Rate |
|---|---|
| Description | Subjects will complete a submaximal treadmill exercise study at baseline. Exercise heart heart, ventilation and perceived exertion will be measured. Subjects will be randomized to MCT or triheptanoin supplementation for 4 months. At the end of treatment, the exercise test will be repeated keeping work performed constant. Change in exercise heart rate, ventilation and exertion will be compared between groups. |
| Time Frame | change from baseline to 4 months of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Medium Chain Triglyceride (MCT) | Triheptanoin |
|---|---|---|
| Arm/Group Description | Subjects randomized to consume 20% of energy from MCT Triheptanoin: Triglyceride with three heptanoin or 7 carbon fatty acids esterified to a glycerol backbone | Subject randomized to consume 20% of energy from triheptanoin. Triheptanoin: Triglyceride with three heptanoin or 7 carbon fatty acids esterified to a glycerol backbone |
| Measure Participants | 16 | 16 |
| Mean (Standard Deviation) [beats per minute] |
-0.1
(9.6)
|
-12.6
(34)
|
Adverse Events
| Time Frame | Four months | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Medium Chain Triglyceride (MCT) | Triheptanoin | ||
| Arm/Group Description | Subjects randomized to consume 20% of energy from MCT Triheptanoin: Triglyceride with three heptanoin or 7 carbon fatty acids esterified to a glycerol backbone | Subject randomized to consume 20% of energy from triheptanoin. Triheptanoin: Triglyceride with three heptanoin or 7 carbon fatty acids esterified to a glycerol backbone | ||
All Cause Mortality |
||||
| Medium Chain Triglyceride (MCT) | Triheptanoin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Medium Chain Triglyceride (MCT) | Triheptanoin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/16 (0%) | 0/16 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Medium Chain Triglyceride (MCT) | Triheptanoin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 12/16 (75%) | 11/16 (68.8%) | ||
| Gastrointestinal disorders | ||||
| Gastrointestinal Upset | 12/16 (75%) | 38 | 11/16 (68.8%) | 24 |
| Diarrhea/Loose stools | 6/16 (37.5%) | 12 | 5/16 (31.3%) | 9 |
| Musculoskeletal and connective tissue disorders | ||||
| Rhabdomyolysis | 4/16 (25%) | 7 | 5/16 (31.3%) | 7 |
| muscle pain/ elevated CPK | 10/16 (62.5%) | 18 | 11/16 (68.8%) | 16 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Melanie Gillingham |
|---|---|
| Organization | Oregon Health & Science University |
| Phone | 503-494-1682 |
| gillingm@ohsu.edu |
- FD003895