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Tiamin som tilleggsterapi for diabetisk ketoacidose

26. mai 2026 oppdatert av: Michael Donnino, Beth Israel Deaconess Medical Center
Dette er en randomisert, dobbeltblind, placebokontrollert studie for å avgjøre om administrering av intravenøs tiamin vil føre til raskere oppløsning av acidose hos pasienter innlagt på sykehus med diabetisk ketoacidose. Etterforskerne vil sekundært undersøke om tiamin forbedrer cellulært oksygenforbruk, forkorter intensivavdeling (ICU) og sykehusopphold eller reduserer ressursutnyttelsen på sykehus.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

Tiamin (vitamin B1) er et vannløselig vitamin som spiller en nøkkelrolle i aerob glukosemetabolisme. Tiamin er en kofaktor av pyruvatdehydrogenase (PDH), et enzym som må aktiveres for å komme inn i Krebs-syklusen for aerob metabolisme. PDH-aktivitet reduseres i tiaminmangeltilstander, noe som resulterer i et skifte i pyruvatmetabolismen til den anaerobe banen. Dette fører til økt laktatproduksjon og acidose. Tiamintap i urinen, med påfølgende tiaminmangel, er ikke uvanlig ved diabetes. Etterforskernes foreløpige studier har funnet at tiaminmangel forekommer hos så mange som 39 % av pasientene med DKA, og at tiaminnivåer er omvendt assosiert med laktat og acidose. Etterforskeren antar at behandling av DKA-pasienter med intravenøs tiamin vil føre til raskere oppløsning av acidose og forbedret aerob metabolisme. Utforskerens sekundære hypotese er at tiaminbehandling vil forkorte opphold på intensivavdelingen og sykehus og føre til utnyttelse av færre sykehusressurser.

I denne randomiserte, dobbeltblinde, placebokontrollerte studien vil pasienter innlagt på sykehus med DKA som er registrert i studien, randomiseres til enten intravenøs tiamin (200 mg i 0,9 % saltvann) to ganger daglig i to dager eller et identisk volum på 0,9 % saltvann på samme tidsplan. Undersøkerens primære resultat er endring i bikarbonat i løpet av 24 timer etter registrering, med målinger ved 0, 6, 12, 18, 24 timer, ved bruk av en lineær modell med blandede effekter. Sekundært vil pasienter bli stratifisert etter Type I og Type II DM. I tillegg vil en forhåndsplanlagt delanalyse av tiaminmangel utføres.

Studietype

Intervensjonell

Registrering (Faktiske)

102

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Forente stater
    • Massachusetts
      • Boston, Massachusetts, Forente stater, 02215
        • Beth Israel Deaconess Medical Center

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Beskrivelse

Inklusjonskriterier:

  • Bikarbonat ≤15 mekv/l
  • Aniongap > 12 mekv/l
  • Blod pH ≤ 7,24 (hvis allerede oppnådd av klinisk team)
  • Urinketoner (kvalitative) eller serumketoner (β-hydroksysmørsyre) > 3 mmol/L
  • Påmelding innen 6 timer etter presentasjon

Ekskluderingskriterier:

  • Nåværende tiamintilskudd ≥ 6 milligram per dag (dvs. mer enn et multivitamin)
  • Konkurrerende årsaker til alvorlig acidose inkludert anfall, karbonmonoksidforgiftning, cyanidtoksisitet, hjertestans, leverdysfunksjon (spesifikt definert som kjent skrumplever)
  • Kjent allergi mot tiamin
  • Konkurrerende indikasjon for tiaminadministrasjon som bedømt av det kliniske teamet (f.eks. alkoholiker)
  • Forskningsbeskyttede populasjoner (gravide kvinner, fanger, utviklingshemmede)
  • Pasient registrert tidligere i samme studie
  • Kodestatus for Ikke gjenopplive/ikke intubere (DNR/DNI) eller Kun komforttiltak (CMO)

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Firemannsrom

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Tiamin
200 mg IV tiamin i 50 ml 0,9 % saltvann to ganger daglig i 2 dager
Legemiddel: 200 mg IV tiamin i 50 ml 0,9 % saltvann
Tiamin 200mg IV hver 12. time i 2 dager
Andre navn:
  • Vitamin B1
Placebo komparator: Placebo
100 ml 0,9 % saltvann to ganger daglig i to dager
Legemiddel: Placebo
50 ml 0,9 % saltvann

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
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
Tiltaksbeskrivelse
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
Tiltaksbeskrivelse
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)

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Beth Israel Deaconess Medical Center

Samarbeidspartnere

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

Etterforskere

  • Hovedetterforsker: Michael Donnino, MD, Beth Israel Deaconess Medical Center

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

21. november 2018

Primær fullføring (Faktiske)

30. september 2024

Studiet fullført (Faktiske)

1. oktober 2024

Datoer for studieregistrering

Først innsendt

22. oktober 2018

Først innsendt som oppfylte QC-kriteriene

22. oktober 2018

Først lagt ut (Faktiske)

24. oktober 2018

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

23. juni 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

26. mai 2026

Sist bekreftet

1. april 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

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

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

NEI

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Ja

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

produkt produsert i og eksportert fra USA

Nei

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