Evidence map›Paper›PMID 36859467›Full record

ArticleScientific reports2023

Maximum dose, safety, tolerability and ketonemia after triheptanoin in glucose transporter type 1 deficiency (G1D).

Ignacio Málaga, Adrian Avila, Sharon Primeaux, Raja Reddy Kallem, Charles R Roe, William C Putnam, Jason Y Park, Shlomo Shinnar, Chul Ahn, Juan M Pascual

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03041363 (Treatment Development of Triheptanoin), which is not on this map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.7field-weighted citation impact, top 31% 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.

NCT03041363 phase1completednot on this map

Treatment Development of Triheptanoin (C7) for Glucose Transporter Type I Deficiency (G1D): A Phase I Maximum Tolerable Dose Trial

TypeinterventionalSponsorJuan PascualRan2017 to 2017Enrolled12ConditionsEpilepsy, GLUT1DS1, Glut1 Deficiency Syndrome 1, Autosomal Recessive, Glucose Metabolism DisordersArmsTriheptanoin
3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Ignacio Málaga *Rare Brain Disorders Program, Department of Neurology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd. Mail Code 8813, Dallas, TX, 75390, USA.
Adrian Avila *Rare Brain Disorders Program, Department of Neurology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd. Mail Code 8813, Dallas, TX, 75390, USA.
Sharon PrimeauxRare Brain Disorders Program, Department of Neurology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd. Mail Code 8813, Dallas, TX, 75390, USA.
Raja Reddy KallemDepartment of Pharmacy Practice and Clinical Pharmacology, Experimental Therapeutics Center, Texas Tech University Health Sciences Center, Dallas, TX, 75235, USA.
Charles R RoeRare Brain Disorders Program, Department of Neurology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd. Mail Code 8813, Dallas, TX, 75390, USA.
William C PutnamDepartment of Pharmacy Practice and Clinical Pharmacology, Experimental Therapeutics Center, Texas Tech University Health Sciences Center, Dallas, TX, 75235, USA.
Jason Y ParkDepartment of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
Shlomo ShinnarDepartments of Neurology and Pediatrics, Albert Einstein College of Medicine, Bronx, NY, 10467, USA.
Chul AhnDepartment of Population and Data Sciences, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
Juan M PascualRare Brain Disorders Program, Department of Neurology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd. Mail Code 8813, Dallas, TX, 75390, USA. Juan.Pascual@utsouthwestern.edu.
The University of Texas Southwestern Medical Center · USTexas Tech University Health Sciences Center · USAlbert Einstein College of Medicine · US

Funding

Dietary treatment of Glut1 deficiency (G1D) - Revision - 1R01NS094257 · NINDS · UT SOUTHWESTERN MEDICAL CENTER · PI PASCUAL, JUAN M. · 2016 to 2021
$4.0M
NINDS NIH HHS NS094257NINDS NIH HHS R01 NS094257
6 · The paper itself

Abstract

Augmentation of anaplerosis, or replenishment of carbon lost during intermediary metabolic transitions, is desirable in energy metabolism defects. Triheptanoin, the triglyceride of 7-carbon heptanoic acid, is anaplerotic via direct oxidation or 5-carbon ketone body generation. In this context, triheptanoin can be used to treat Glucose transporter type 1 deficiency encephalopathy (G1D). An oral triheptanoin dose of 1 g/Kg/day supplies near 35% of the total caloric intake and impacted epilepsy and cognition in G1D. This provided the motivation to establish a maximum, potentially greater dose. Using a 3 + 3 dose-finding approach useful in oncology, we studied three age groups: 4-6, 6.8-10 and 11-16 years old. This allowed us to arrive at a maximum tolerated dose of 45% of daily caloric intake for each group. Safety was ascertained via analytical blood measures. One dose-limiting toxicity, occurring in 1 of 6 subjects, was encountered in the middle age group in the context of frequently reduced gastrointestinal tolerance for all groups. Ketonemia following triheptanoin was determined in another group of G1D subjects. In them, β-ketopentanoate and β-hydroxypentanoate concentrations were robustly but variably increased. These results enable the rigorous clinical investigation of triheptanoin in G1D by providing dosing and initial tolerability, safety and ketonemic potential.ClinicalTrials.gov registration: NCT03041363, first registration 02/02/2017.

Indexed as

KetosisCarbonChild, PreschoolGlucose Transporter Type 1HumansMiddle AgedTriglyceridesCarbonGlucose Transporter Type 1Triglyceridestriheptanoin

Identifiers

PMID36859467
PMCPMC9977760
OpenAlexW4322738992

What OpenQuestion holds

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LicenceCC BY
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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.