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Thiamin som supplerende terapi for diabetisk ketoacidose

26. maj 2026 opdateret af: Michael Donnino, Beth Israel Deaconess Medical Center
Dette er et randomiseret, dobbeltblindt, placebokontrolleret forsøg for at afgøre, om administration af intravenøs thiamin vil føre til hurtigere opløsning af acidose hos patienter indlagt på hospitalet med diabetisk ketoacidose. Efterforskerne vil sekundært undersøge, om thiamin forbedrer cellulært iltforbrug, forkorter intensivafdeling (ICU) og hospitalsophold eller reducerer hospitalsressourceudnyttelsen.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

Thiamin (vitamin B1) er et vandopløseligt vitamin, der spiller en nøglerolle i aerob glukosemetabolisme. Thiamin er en co-faktor af pyruvat dehydrogenase (PDH), et enzym, der skal aktiveres for at komme ind i Krebs cyklus for aerob metabolisme. PDH-aktivitet reduceres i thiaminmangeltilstande, hvilket resulterer i et skift i pyruvatmetabolismen til den anaerobe vej. Dette fører til øget laktatproduktion og acidose. Thiamintab i urinen med deraf følgende thiaminmangel er ikke ualmindeligt ved diabetes. Efterforskernes foreløbige undersøgelser har fundet, at thiaminmangel i forekommer hos hele 39 % af patienterne med DKA, og at thiaminniveauer er omvendt forbundet med laktat og acidose. Efterforskeren antager, at behandling af DKA-patienter med intravenøs thiamin vil føre til hurtigere opløsning af acidose og forbedret aerob metabolisme. Investigatorens sekundære hypotese er, at thiaminbehandling vil forkorte ophold på intensivafdelingen og hospitalet og føre til udnyttelse af færre hospitalsressourcer.

I dette randomiserede, dobbeltblindede, placebokontrollerede forsøg vil patienter indlagt på hospitalet med DKA, som er inkluderet i undersøgelsen, blive randomiseret til enten intravenøs thiamin (200 mg i 0,9 % saltvand) to gange dagligt i to dage eller et identisk volumen på 0,9 % saltvand på samme tidsplan. Undersøgerens primære resultat er ændring i bikarbonat i løbet af de 24 timer efter tilmelding, med målinger ved 0, 6, 12, 18, 24 timer ved brug af en lineær mixed-effects model. Sekundært vil patienter blive stratificeret efter Type I og Type II DM. Derudover vil der blive udført en forudplanlagt delanalyse af forsøgspersoner med thiaminmangel.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

102

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Forenede Stater
    • Massachusetts
      • Boston, Massachusetts, Forenede Stater, 02215
        • Beth Israel Deaconess Medical Center

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Beskrivelse

Inklusionskriterier:

  • Bicarbonat ≤15 mEq/L
  • Aniongab > 12 mEq/L
  • Blod pH ≤ 7,24 (hvis allerede opnået af klinisk hold)
  • Urinketoner (kvalitativ) eller serumketoner (β-hydroxysmørsyre) > 3 mmol/L
  • Tilmelding senest 6 timer efter præsentationen

Ekskluderingskriterier:

  • Nuværende tiamintilskud ≥ 6 milligram om dagen (dvs. mere end et multivitamin)
  • Konkurrerende årsager til svær acidose, herunder anfald, kulilteforgiftning, cyanidtoksicitet, hjertestop, leverdysfunktion (specifikt defineret som kendt cirrhose)
  • Kendt allergi over for thiamin
  • Konkurrerende indikation for thiaminadministration vurderet af det kliniske team (f.eks. alkoholiker)
  • Forskningsbeskyttede befolkninger (gravide kvinder, fanger, intellektuelt handicappede)
  • Patient indskrevet tidligere i samme undersøgelse
  • Kodestatus for Må ikke genoplives/må ikke intuberes (DNR/DNI) eller kun komfortforanstaltninger (CMO)

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Firedobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Thiamin
200mg IV thiamin i 50mL 0,9% saltvand to gange dagligt i 2 dage
Medicin: 200mg IV thiamin i 50mL 0,9% saltvand
Thiamin 200mg IV hver 12. time i 2 dage
Andre navne:
  • Vitamin B1
Placebo komparator: Placebo
100 ml 0,9 % saltvand to gange dagligt i to dage
Medicin: Placebo
50 ml 0,9% saltvand

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Plasma Bicarbonate Levels
Tidsramme: 6, 12, 18, and 24 hours after enrollment
Primary outcome of plasma bicarbonate levels over 24 hours (6, 12, 18, 24 hours) following enrollment
6, 12, 18, and 24 hours after enrollment

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Lactate
Tidsramme: 6, 12, 18, and 24 hours after enrollment
Secondary outcome of lactate over 24 hours (6, 12, 18, 24 hours) following enrollment
6, 12, 18, and 24 hours after enrollment
Anion Gap
Tidsramme: 6, 12, 18, and 24 hours after enrollment
Secondary outcome of anion gap over 24 hours (6, 12, 18, 24 hours) following enrollment
6, 12, 18, and 24 hours after enrollment
ICU Length of Stay
Tidsramme: 45 days
ICU length of stay reflects the number of ICU admission days.
45 days
Hospital Length of Stay
Tidsramme: 45 days
Hospital length of stay reflects how long it takes a diabetic ketoacidosis patient to recover to the point where he/she can be released from the hospital.
45 days
Duration of Insulin Therapy
Tidsramme: First 7 days after enrollment
The duration of insulin therapy is calculated by examining the hospital clinical information systems for all records of IV insulin infusion beginning at the time of enrollment. The start and the stop time-stamps of medication infusion are used to calculate a duration of infusion.
First 7 days after enrollment
SOFA Score (Sequential Organ Failure Assessement Score)
Tidsramme: 24 hours
The SOFA score is a validated measure of organ dysfunction commonly used in critically ill patients, particularly those with sepsis. It evaluates the function of six organ systems-respiratory, cardiovascular, neurologic, hepatic, renal, and coagulation-based on routinely collected clinical and laboratory data. Each organ system is assigned a score from 0 (normal function) to 4 (most severe dysfunction), resulting in a total score ranging from 0 to 24. Higher SOFA scores indicate greater severity of organ failure and a higher risk of adverse outcomes. SOFA score in this study uses a modification in which the arterial oxygen saturation/fraction of inspired oxygen (SaO2 /FiO2) ratio is substituted for the partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2 /FiO2 ratio).
24 hours
Oxygen Consumption by Circulating Mononuclear Cells
Tidsramme: 24 hours
Oxygen consumption rate of circulating peripheral blood mononuclear cells measured using Seahorse. Basal respiration represents oxygen consumption under baseline conditions. ATP-linked respiration represents oxygen consumption coupled to ATP production, while proton leak represents oxygen consumption not linked to ATP synthesis. Maximal respiration represents the maximal capacity of the electron transport chain after uncoupling. Spare respiratory capacity represents the difference between maximal and basal respiration and indicates the ability to respond to increased energy demand. Non-mitochondrial respiration represents oxygen consumption independent of mitochondrial activity.
24 hours
Pyruvate Dehydrogenase Activity
Tidsramme: 24 hours and 72 hours (or at discharge if hostpial length of stay was less than 72 hours)
Secondary outcome of change in PDH specific activity over 72 hours or at discharge if patient's hospital length of stay was less than 72 hours. PDH activity and total PDH protein quantity were measured in isolated peripheral blood mononuclear cells (PBMCs) following selective disruption of the mitochondrial membrane, using a previously validated immunocapture and microplate-based enzymatic assay protocol. PDH-specific activity was calculated as the ratio of measured PDH enzymatic activity to the natural logarithm of PDH protein quantity (PDH activity / ln[PDH quantity]), providing a normalized metric that reflects the functional efficiency of the enzyme independent of its expression level. Higher values suggest higher enzymatic efficiency.
24 hours and 72 hours (or at discharge if hostpial length of stay was less than 72 hours)
Neurocognitive: Hopkins Verbal Learning Test - Total Recall
Tidsramme: At hospital discharge, median of 4 days
The Hopkins Verbal Learning Test-Revised (HVLT-R) Total Recall score is a measure of verbal learning and immediate memory. Participants are read a list of 12 words (from three semantic categories) and asked to recall as many words as possible across three consecutive learning trials. The Total Recall score is calculated as the sum of correctly recalled words across the three trials, yielding a possible range of 0 to 36, with higher scores indicating better verbal learning and memory performance. This score reflects both initial acquisition and short-term retention of verbal information and is commonly used to assess cognitive function in clinical research.
At hospital discharge, median of 4 days
Neurocognitive: Hopkins Verbal Learning Test - Delayed Recall
Tidsramme: At hospital discharge, median of 4 days
The Hopkins Verbal Learning Test-Revised (HVLT-R) Delayed Recall score assesses retention of verbal information after a delay. Following completion of the three learning trials, participants are asked to recall the previously presented word list after a delay period (typically 20-25 minutes) without re-exposure to the words. The Delayed Recall score is calculated as the number of correctly recalled words, with a possible range of 0 to 12, where higher scores indicate better memory retention. This measure reflects the ability to consolidate and retrieve learned information over time and is commonly used to evaluate memory function in clinical and research settings.
At hospital discharge, median of 4 days
Neurocognitive: Hopkins Verbal Learning Test - Retention
Tidsramme: At hospital discharge, median of 4 days
The Hopkins Verbal Learning Test-Revised (HVLT-R) Retention (%) score reflects the proportion of learned information that is retained over a delay. It is calculated as the ratio of the Delayed Recall score to the highest number of words recalled on any of the three immediate recall trials, multiplied by 100, yielding a percentage value. Scores typically range from 0% to 100%, with higher values indicating better retention of previously learned material. This measure provides an index of memory retention independent of initial learning performance.
At hospital discharge, median of 4 days
Neurocognitive: Hopkins Verbal Learning Test - Recognition Discrimination Index
Tidsramme: At hospital discharge, median of 4 days
The Hopkins Verbal Learning Test-Revised (HVLT-R) Recognition Discrimination Index assesses recognition memory by evaluating the ability to distinguish previously learned words from novel distractors. During the recognition phase, participants are presented with a list of target words and distractor words and asked to identify those that were previously learned. The Recognition Discrimination Index is calculated as the number of true positives (correctly identified target words) minus the number of false positives (incorrectly identified distractor words), yielding a score typically ranging from -12 to 12. Higher scores indicate better recognition accuracy and discrimination ability, reflecting the integrity of memory retrieval processes.
At hospital discharge, median of 4 days
Neurocognitive: Brief Visuospatial Memory Test
Tidsramme: At hospital discharge, median of 4 days
The Brief Visuospatial Memory Test (BVMT) assesses visuospatial learning and memory. Participants are shown six geometric designs for a brief period and asked to reproduce them from memory across three learning trials. Performance is scored based on the accuracy and placement of each design, with a total recall score ranging from 0 to 36, where higher scores indicate better visuospatial memory. A delayed recall trial is administered after a delay to assess retention of visual information. This measure evaluates the ability to encode, store, and retrieve visuospatial material.
At hospital discharge, median of 4 days
Neurocognitive: Trail Making Test - Test Part A
Tidsramme: At hospital discharge, median of 4 days
The Trail Making Test Part A (TMT-A) assesses visual attention, processing speed, and psychomotor function. Participants are instructed to connect numbered circles in sequential order as quickly as possible. The primary outcome is the time to completion, measured in seconds, with lower times indicating better performance. There is no fixed maximum score, although testing is typically discontinued at a predefined time limit (commonly 300 seconds).
At hospital discharge, median of 4 days
Neurocognitive: Trail Making Test - Test Part B
Tidsramme: At hospital discharge, median of 4 days
The Trail Making Test Part B (TMT-B) assesses executive function, including cognitive flexibility and set-shifting, in addition to processing speed. Participants are required to alternate between numbers and letters in sequence (e.g., 1-A-2-B) as quickly as possible. The primary outcome is the time to completion, measured in seconds, with lower times indicating better performance. As with TMT-A, there is no fixed maximum score, and testing is typically discontinued at a predefined time limit (commonly 300 seconds).
At hospital discharge, median of 4 days
Neurocognitive: WAIS-IV Digit Span
Tidsramme: At hospital discharge, median of 4 days
The Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) Digit Span subtest assesses attention, working memory, and concentration. Participants are asked to repeat sequences of numbers in forward order (Digit Span Forward), reverse order (Digit Span Backward), and ascending order (Digit Span Sequencing). Scores are based on the total number of correctly recalled sequences, with higher scores indicating better attention and working memory capacity. The total score ranges from 0 to 48.
At hospital discharge, median of 4 days
Neurocognitive: Test of Verbal Fluency and Animal Naming
Tidsramme: At hospital discharge, median of 4 days
The Animal Naming test is a measure of semantic verbal fluency and executive function. Participants are asked to name as many animals as possible within a fixed time period. The score is the total number of unique, correct animal names generated, with higher scores indicating better semantic memory retrieval and executive functioning. Scores range from 0 with no fixed upper limit.
At hospital discharge, median of 4 days
Neurocognitive: Test of Premorbid Functioning
Tidsramme: At hospital discharge, median of 4 days
The Test of Premorbid Functioning (TOPF) estimates an individual's baseline cognitive ability prior to illness or injury. Participants are asked to read aloud a list of irregularly spelled words, and performance is scored based on correct pronunciation. Scores are used to estimate premorbid intellectual functioning. Scores range from 0 to 70, with higher scores indicating higher estimated premorbid functioning. This measure helps contextualize current cognitive performance relative to expected baseline levels.
At hospital discharge, median of 4 days

Andre resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
C-peptide Levels
Tidsramme: 0, 24 hours, and 72 hours (or at discharge if hospital length of stay was less than 72 hours)
C-peptide levels measured at time of study drug administration, 24 hours, and at 72 hours (or at discharge if hospital length of stay was less than 72 hours).
0, 24 hours, and 72 hours (or at discharge if hospital length of stay was less than 72 hours)

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Beth Israel Deaconess Medical Center

Samarbejdspartnere

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Efterforskere

  • Ledende efterforsker: Michael Donnino, MD, Beth Israel Deaconess Medical Center

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

21. november 2018

Primær færdiggørelse (Faktiske)

30. september 2024

Studieafslutning (Faktiske)

1. oktober 2024

Datoer for studieregistrering

Først indsendt

22. oktober 2018

Først indsendt, der opfyldte QC-kriterier

22. oktober 2018

Først opslået (Faktiske)

24. oktober 2018

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

23. juni 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

26. maj 2026

Sidst verificeret

1. april 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • 2018P000475
  • 1R01DK112886-01A1 (U.S. NIH-bevilling/kontrakt)

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

INGEN

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

produkt fremstillet i og eksporteret fra U.S.A.

Ingen

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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