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Tiamin som tilläggsterapi för diabetisk ketoacidos

26 maj 2026 uppdaterad av: Michael Donnino, Beth Israel Deaconess Medical Center
Detta är en randomiserad, dubbelblind, placebokontrollerad studie för att avgöra om administrering av intravenös tiamin kommer att leda till snabbare upplösning av acidos hos patienter som lagts in på sjukhus med diabetisk ketoacidos. Utredarna kommer i andra hand att undersöka om tiamin förbättrar cellulär syreförbrukning, förkortar intensivvårdsavdelning (ICU) och sjukhusvistelse eller minskar resursutnyttjandet på sjukhus.

Studieöversikt

Status

Avslutad

Betingelser

Intervention / Behandling

Detaljerad beskrivning

Tiamin (vitamin B1) är ett vattenlösligt vitamin som spelar en nyckelroll i aerob glukosmetabolism. Tiamin är en kofaktor för pyruvatdehydrogenas (PDH), ett enzym som måste aktiveras för inträde i Krebs-cykeln för aerob metabolism. PDH-aktivitet reduceras i tiaminbristtillstånd, vilket resulterar i en förskjutning i pyruvatmetabolismen till den anaeroba vägen. Detta leder till ökad laktatproduktion och acidos. Tiaminförlust i urinen, med åtföljande tiaminbrist, är inte ovanligt vid diabetes. Utredarnas preliminära studier har funnit att tiaminbrist förekommer hos så många som 39 % av patienterna med DKA, och att tiaminnivåerna är omvänt associerade med laktat och acidos. Utredaren antar att behandling av DKA-patienter med intravenös tiamin kommer att leda till snabbare upplösning av acidos och förbättrad aerob metabolism. Utredarens sekundära hypotes är att tiaminbehandling kommer att förkorta vistelser på ICU och sjukhus och leda till att färre sjukhusresurser tas tillvara.

I denna randomiserade, dubbelblinda, placebokontrollerade studie kommer patienter inlagda på sjukhuset med DKA och som ingår i studien att randomiseras till antingen intravenös tiamin (200 mg i 0,9 % koksaltlösning) två gånger dagligen i två dagar eller en identisk volym av 0,9 % koksaltlösning på samma schema. Utredarens primära resultat är förändring av bikarbonat under de 24 timmarna efter inskrivningen, med mätningar vid 0, 6, 12, 18, 24 timmar, med hjälp av en linjär modell med blandade effekter. Sekundärt kommer patienter att stratifieras med typ I och typ II DM. Dessutom kommer en förplanerad delanalys av patienter med tiaminbrist att utföras.

Studietyp

Interventionell

Inskrivning (Faktisk)

102

Fas

  • Fas 2

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

  • Förenta staterna
    • Massachusetts
      • Boston, Massachusetts, Förenta staterna, 02215
        • Beth Israel Deaconess Medical Center

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år och äldre (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Beskrivning

Inklusionskriterier:

  • Bikarbonat ≤15 mekv/l
  • Anjongap > 12 mekv/l
  • Blodets pH ≤ 7,24 (om redan erhållits av kliniskt team)
  • Urinketoner (kvalitativa) eller serumketoner (β-hydroxismörsyra) > 3 mmol/L
  • Anmälan inom 6 timmar efter presentation

Exklusions kriterier:

  • Nuvarande tiamintillskott ≥ 6 milligram per dag (dvs mer än ett multivitamin)
  • Konkurrerande orsaker till svår acidos inklusive krampanfall, kolmonoxidförgiftning, cyanidtoxicitet, hjärtstillestånd, leverdysfunktion (specifikt definierad som känd cirros)
  • Känd allergi mot tiamin
  • Konkurrerande indikation för tiaminadministrering enligt bedömning av det kliniska teamet (t.ex. alkoholist)
  • Forskningsskyddade befolkningar (gravida kvinnor, fångar, intellektuellt funktionshindrade)
  • Patient inskriven tidigare i samma studie
  • Kodstatus för Återuppliva inte/Intubera inte (DNR/DNI) eller Endast komfortåtgärder (CMO)

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Fyrdubbla

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: Tiamin
200 mg IV tiamin i 50 ml 0,9 % koksaltlösning två gånger dagligen i 2 dagar
Läkemedel: 200mg IV tiamin i 50mL 0,9% koksaltlösning
Tiamin 200mg IV var 12:e timme i 2 dagar
Andra namn:
  • Vitamin B1
Placebo-jämförare: Placebo
100 ml 0,9 % koksaltlösning två gånger dagligen i två dagar
Läkemedel: Placebo
50 ml 0,9 % koksaltlösning

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Plasma Bicarbonate Levels
Tidsram: 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

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Lactate
Tidsram: 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
Tidsram: 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
Tidsram: 45 days
ICU length of stay reflects the number of ICU admission days.
45 days
Hospital Length of Stay
Tidsram: 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
Tidsram: 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)
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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

Andra resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
C-peptide Levels
Tidsram: 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)

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Beth Israel Deaconess Medical Center

Samarbetspartners

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

Utredare

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

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Allmänna publikationer

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

21 november 2018

Primärt slutförande (Faktisk)

30 september 2024

Avslutad studie (Faktisk)

1 oktober 2024

Studieregistreringsdatum

Först inskickad

22 oktober 2018

Först inskickad som uppfyllde QC-kriterierna

22 oktober 2018

Första postat (Faktisk)

24 oktober 2018

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

23 juni 2026

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

26 maj 2026

Senast verifierad

1 april 2026

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

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

Plan för individuella deltagardata (IPD)

Planerar du att dela individuella deltagardata (IPD)?

NEJ

Läkemedels- och apparatinformation, studiedokument

Studerar en amerikansk FDA-reglerad läkemedelsprodukt

Ja

Studerar en amerikansk FDA-reglerad produktprodukt

Nej

produkt tillverkad i och exporterad från U.S.A.

Nej

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