Evidence map›Paper›PMID 28871440›Full record

Trial reportJournal of inherited metabolic disease2017

Triheptanoin versus trioctanoin for long-chain fatty acid oxidation disorders: a double blinded, randomized controlled trial.

Melanie B Gillingham, Stephen B Heitner, Julie Martin, Sarah Rose, Amy Goldstein, Areeg Hassan El-Gharbawy, Stephanie Deward, Michael R Lasarev, Jim Pollaro, James P DeLany and 6 more

2 registry-linked trialsOpen access · greenAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of inherited metabolic disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 61 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 3 pooled it
7.7field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01379625 phase2completednot on this map

Phase 2 Study of Triheptanoin for Treatment of Long-Chain Fatty Acid Oxidation Disorders

TypeinterventionalSponsorOregon Health and Science UniversityRan2011 to 2015Enrolled32ConditionsVery Long-chain acylCoA Dehydrogenase (VLCAD) Deficiency, Carnitine Palmitoyltransferase 2 (CPT2) Deficiency, Mitochondrial Trifunctional Protein (TFP) Deficiency, Long-chain 3 hydroxyacylCoA Dehydrogenase (LCHAD) DeficiencyArmsTriheptanoin
NCT04513002 phase2completednot on this mapstarted 2022, after this paper: background citation

A Phase 2A/2B Placebo-controlled Randomised Clinical Trial to Test the Ability of Triheptanoin to Protect Primary Airway Epithelial Cells Obtained From Participants With Ataxia-telangiectasia Against Death Induced by Glucose Deprivation

TypeinterventionalSponsorThe University of QueenslandRan2022 to 2023Enrolled30ConditionsAtaxia TelangiectasiaArmsTriheptanoin
3 · Its place in the literature

Who cites it

61 citing papers in PubMed, 3 syntheses or guidelines pooled it, 109 citations in OpenAlex.

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  7. No effect of triheptanoin on exercise performance in McArdle disease.Annals of clinical and translational neurology · 2019
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1 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 7 institutions in 2 countries.

Melanie B GillinghamDepartment of Molecular and Medical Genetics, Graduate Programs in Human Nutrition, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA. gillingm@ohsu.edu.
Stephen B HeitnerKnight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA.
Julie MartinDepartment of Molecular and Medical Genetics, Graduate Programs in Human Nutrition, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA.
Sarah RoseDepartment of Molecular and Medical Genetics, Graduate Programs in Human Nutrition, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA.
Amy GoldsteinNeurogenetics and Metabolism, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA.
Areeg Hassan El-GharbawyDivision of Medical Genetics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
Stephanie DewardDivision of Medical Genetics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
Michael R LasarevCenter for Research on Occupational and Environmental Toxicology, Oregon Health & Science University, Portland, OR, USA.
Jim PollaroAdvanced Imaging Research Center, Oregon Health & Science University, Portland, OR, USA.
James P DeLanyDepartment of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Luke J BurchillKnight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA.
Bret GoodpasterDepartment of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
James ShoemakerDepartment of Biochemistry and Molecular Biology, Saint Louis University, Saint Louis, MO, USA.
Dietrich MaternLaboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Cary O HardingDepartment of Molecular and Medical Genetics, Graduate Programs in Human Nutrition, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA.
Jerry VockleyDivision of Medical Genetics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
Oregon Health & Science University · USChildren's Hospital of Pittsburgh · USUniversity of Pittsburgh · USAdvanced Imaging Research (United States) · USMayo Clinic in Arizona · USPRA Health Sciences · USSaint Louis University · ES

Funding

University of Pittsburgh Clinical and Translational Science InstituteUL1TR001857 · NCATS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E · 2016 to 2025
$129.3M
Oregon Clinical and Translational Research InstituteUL1TR000128 · NCATS · OREGON HEALTH & SCIENCE UNIVERSITY · PI ELLISON, DAVID H · 2012 to 2015
$28.7M
EXITO: Enhancing Cross-disciplinary Infrastructure and Training at OregonUL1GM118964 · NIGMS · PORTLAND STATE UNIVERSITY · PI KELLER, THOMAS E · 2015 to 2023
$18.0M
EXITO: Enhancing Cross-disciplinary Infrastructure and Training at OregonRL5GM118963 · NIGMS · PORTLAND STATE UNIVERSITY · PI KELLER, THOMAS E · 2015 to 2023
$11.9M
EXITO: Enhancing Cross-disciplinary Infrastructure and Training at OregonTL4GM118965 · NIGMS · PORTLAND STATE UNIVERSITY · PI KELLER, THOMAS E · 2015 to 2022
$10.1M
Inborn Errors of Long Chain Fat MetabolismR01DK078775 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI VOCKLEY, GERARD · 2008 to 2019
$4.5M
Ph 2 Study of Triheptanoin for Tx of Long-Chain Fatty Acid Oxidation DisorderR01FD003895 · FDA · OREGON HEALTH & SCIENCE UNIVERSITY · PI GILLINGHAM, MELANIE B · 2011 to 2014
$1.2M
FDA HHS R01 FD003895NCATS NIH HHS UL1 TR000128NCATS NIH HHS UL1 TR001857NIDDK NIH HHS R01 DK078775NIGMS NIH HHS RL5 GM118963NIGMS NIH HHS TL4 GM118965NIGMS NIH HHS UL1 GM118964
6 · The paper itself

Abstract

backgroundObservational reports suggest that supplementation that increases citric acid cycle intermediates via anaplerosis may have therapeutic advantages over traditional medium-chain triglyceride (MCT) treatment of long-chain fatty acid oxidation disorders (LC-FAODs) but controlled trials have not been reported. The goal of our study was to compare the effects of triheptanoin (C7), an anaplerotic seven-carbon fatty acid triglyceride, to trioctanoin (C8), an eight-carbon fatty acid triglyceride, in patients with LC-FAODs.

methodsA double blinded, randomized controlled trial of 32 subjects with LC-FAODs (carnitine palmitoyltransferase-2, very long-chain acylCoA dehydrogenase, trifunctional protein or long-chain 3-hydroxy acylCoA dehydrogenase deficiencies) who were randomly assigned a diet containing 20% of their total daily energy from either C7 or C8 for 4 months was conducted. Primary outcomes included changes in total energy expenditure (TEE), cardiac function by echocardiogram, exercise tolerance, and phosphocreatine recovery following acute exercise. Secondary outcomes included body composition, blood biomarkers, and adverse events, including incidence of rhabdomyolysis.

resultsPatients in the C7 group increased left ventricular (LV) ejection fraction by 7.4% (p = 0.046) while experiencing a 20% (p = 0.041) decrease in LV wall mass on their resting echocardiogram. They also required a lower heart rate for the same amount of work during a moderate-intensity exercise stress test when compared to patients taking C8. There was no difference in TEE, phosphocreatine recovery, body composition, incidence of rhabdomyolysis, or any secondary outcome measures between the groups.

conclusionsC7 improved LV ejection fraction and reduced LV mass at rest, as well as lowering heart rate during exercise among patients with LC-FAODs. CLINICAL

trial registrationClinicaltrials.gov NCT01379625.

Indexed as

Acyl-CoA Dehydrogenase, Long-ChainAdolescentAdultCaprylatesCardiomyopathiesCarnitineChildDietary FatsDouble-Blind MethodExerciseFatty AcidsFemaleHumansLipid Metabolism, Inborn ErrorsMaleMiddle AgedAcyl-CoA Dehydrogenase, Long-ChainCaprylatesCarnitineDietary FatsFatty AcidsMitochondrial Trifunctional ProteintricaprylinTriglyceridestriheptanoin

Identifiers

PMID28871440
PMCPMC6545116
OpenAlexW2751445216

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.