CGM-guided Patch Pump vs Basal-Bolus Injection for Steroid-Induced Hyperglycemia in Sudden Sensorineural Hearing Loss: SHIP Trial (SHIP)
Steroid-induced Hyperglycemia Management With Insulin Patch Pump in Sudden Sensorineural Hearing Loss: a CGM-guided Exploratory Randomized Controlled Trial (SHIP Trial)
This exploratory randomized controlled trial evaluates whether a CGM-guided temporary patch pump (CareLevo CSII) reduces glucocorticoid-induced hyperglycemia (GIH) compared to a Lantus-based basal-bolus injection (MDI) regimen in patients with sudden sensorineural hearing loss (SSNHL) and type 2 diabetes or prediabetes receiving high-dose systemic corticosteroids (methylprednisolone 48 mg/day).
Patients with SSNHL are treated with high-dose oral corticosteroids as standard of care, which often causes significant postprandial hyperglycemia - particularly in patients with pre-existing diabetes or prediabetes. No randomized trial has investigated the optimal insulin delivery strategy for this specific clinical scenario.
All enrolled participants undergo a 2-night inpatient admission (Day 1-3) for safe insulin initiation and device education, followed by outpatient management (Day 4-14). All participants wear a CareSens Air continuous glucose monitor (CGM, 15-day sensor) throughout Day 1-14.
Participants meeting insulin activation criteria are randomized 1:1 to:
- Arm A (CSII): CareLevo patch pump using a steroid-wave basal profile and carbohydrate-band meal bolus via the app's bolus calculator (CGM-integrated, IOB-adjusted)
- Arm B (MDI): Insulin glargine U-100 (Lantus) qAM plus Fiasp prandial bolus via pen using a pre-printed dose table with identical carbohydrate-band algorithm
Both arms use identical glycemic targets, carbohydrate-band bolus algorithm (ICR/ISF identical), and correction rules. The primary difference is insulin delivery (patch pump vs. pen injection) and basal profile (steroid-wave CSII vs. flat glargine). The primary outcome is 24-hour CGM Time Above Range (TAR) >180 mg/dL averaged over the 9-day high-dose steroid period (Day 1-9).
Přehled studie
Postavení
Detailní popis
BACKGROUND SSNHL is treated with high-dose systemic corticosteroids (methylprednisolone 48 mg/day, prednisolone-equivalent 60 mg/day). In patients with diabetes or prediabetes, GIH is characterized by afternoon-to-evening postprandial predominance. Despite guideline recommendations for insulin-based management, no randomized evidence exists to guide optimal insulin delivery for this short-term, high-dose steroid course. ADA Standards of Care 2026 acknowledges glargine- or NPH-based basal-bolus insulin as established approaches for GIH; however, neither addresses the potential advantage of steroid-wave basal profiling achievable with CSII.
STUDY DESIGN Single-center, open-label, exploratory RCT. Day 1-3: 2-night inpatient admission. Day 4-14: outpatient management with fixed discharge dosing plan provided at Day 3.
STEROID PROTOCOL (standard of care):
Day 1-9: Methylprednisolone 48 mg/day | Day 10-11: 32 mg/day | Day 12-13: 16 mg/day | Day 14: 8 mg/day | Day 15~: discontinuation
CGM:
All participants: CareSens Air CGM (i-SENS, South Korea), 15-day sensor, attached on Day 0 (study-funded). CGM data collected Day 1-14. Primary endpoint computed from Day 1-9 24-hour data. Steroid-wave window (10:00-22:00) TAR is a pre-specified key secondary endpoint.
INSULIN PROTOCOLS - COMMON ELEMENTS:
Initial study TDD: 0.35-0.40 U/kg/day (T2DM insulin-naïve, PE ≥60 mg/day); 0.20-0.25 U/kg/day (prediabetes). Upper limit: 0.50 U/kg/day or 60 U/day.
Basal budget: 35-45% of study TDD for both arms (delivery method differs). Carbohydrate-band meal bolus: Patients select from 6 meal-size categories (0/30/45/60/75/90g). ICR: breakfast ~45g/(0.15×TDD); lunch/dinner ~60g/(0.20×TDD). Identical algorithm for both arms.
Correction: ISF = 1500/TDD (daytime); 2×ISF (nighttime). Fixed correction table provided at discharge (calculated once; not recalculated during outpatient period). No routine post-meal correction. Rescue correction only: ≥3h after last bolus, sustained POC/CGM ≥300 mg/dL.
Arm A (CSII): CareLevo patch pump with fast-acting insulin aspart (Fiasp). Steroid-wave basal profile: 00:00-04:00 8%, 04:00-07:00 12%, 07:00-10:00 15%, 10:00-16:00 35%, 16:00-22:00 25%, 22:00-24:00 5% of basal budget. Bolus calculator integrated with CGM; patient selects carbohydrate band. IOB reflected in all bolus calculations. Patch replaced Day 8.
Arm B (MDI): Insulin glargine U-100 (Lantus) qAM = 45% of TDD, administered with morning steroid. Fiasp prandial bolus via insulin pen using pre-printed dose table (same carbohydrate-band algorithm as Arm A). Fixed correction table provided at discharge.
SAMPLE SIZE:
44 participants (22 per arm). Two-sided α=0.05, 80% power, assumed Δ=15%p (MDI TAR=55%, CSII TAR=40%), SD=16%, 20% dropout (Cohen's d=0.94). ANCOVA covariates: baseline POC glucose, HbA1c, diabetes category, BMI.
Typ studie
Zápis (Odhadovaný)
Fáze
- Nelze použít
Kontakty a umístění
Studijní kontakt
- Jméno: Hun Jee Choe MD, PhD
- Telefonní číslo: +82-10-9493-5703
- E-mail: hunjeechoe@gmail.com
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dospělý
- Starší dospělý
Přijímá zdravé dobrovolníky
Popis
Inclusion Criteria:
- Age ≥19 years
- Idiopathic SSNHL: ≥30 dB sensorineural hearing loss across ≥3 consecutive frequencies within 72 hours
- Affected ear PTA4 (mean of 0.5/1/2/4 kHz) ≥40 dB HL (moderate or greater)
- Planned methylprednisolone 48 mg/day orally once in the morning
- At least one of: known T2DM; HbA1c 5.7-10.0% within 3 months; POC glucose ≥140 mg/dL ×2 (≥2h apart, ≥1 postprandial) within 24h of steroid
- If on prior insulin: outpatient TDD ≤30 U/day
- Able to eat ≥2 meals/day, wear CGM and patch pump, use smartphone
- Willing to undergo 2-night inpatient admission (Day 1-3)
- Written informed consent
Exclusion Criteria:
- Type 1 DM, LADA, pancreatogenic DM, DKA/HHS within 12 months, ketonuria at enrollment
- Enrollment POC ≥350 mg/dL or immediate IV insulin requirement
- HbA1c ≥10.0%
- eGFR <30 mL/min/1.73m² or dialysis
- Pregnancy/breastfeeding; women of childbearing potential: positive urine hCG
- ICU, sepsis, NPO, TPN/enteral nutrition
- Severe hepatic failure (Child-Pugh C)
- Dexamethasone, divided-dose, or pulse steroids planned
- Prior CSII or AID device user
- Skin adhesive allergy precluding CGM or patch pump use
- Insufficient cognitive function for device or dosing table use
- Planned MRI requiring repeated CGM/pump removal
- PTA >70 dB (profound hearing loss requiring combined intratympanic steroid)
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Experimentální: CareLevo CSII (Arm A)
Participants are fitted with the CareLevo patch pump loaded with Fiasp.
A steroid-wave basal profile concentrates insulin delivery during afternoon-evening (10:00-22:00) to match methylprednisolone pharmacodynamics, while minimizing overnight basal.
Meal bolus uses a carbohydrate-band calculator integrated with CareSens Air CGM.
IOB is reflected in all bolus decisions.
Patch replaced Day 8. Insulin tapered proportionally to steroid reduction from Day 10.
|
CareLevo (CareMedi Inc., South Korea): tubeless patch pump, 300U reservoir, max 7-day wear, basal 0.05-15 U/hr, bolus 0.05-25 U, CareSens Air CGM integration via smartphone app.
Steroid-wave basal profile (highest during 10:00-16:00, 35% of basal budget).
App bolus calculator accepts CGM glucose + patient-selected carbohydrate band (0/30/45/60/75/90g) and computes dose based on ICR, ISF, and IOB.
Provided free by manufacturer (CareMedi); manufacturer has no role in study design, data analysis, or publication.
Fiasp used as prandial and correction insulin in both arms.
Meal bolus via carbohydrate-band selection (0/30/45/60/75/90g).
ICR: breakfast 45g/(0.15×TDD);
lunch/dinner 60g/(0.20×TDD).
ISF = 1500/TDD (daytime), 2×ISF (night).
Arm A: app auto-calculation with IOB.
Arm B: pre-printed dose table (same algorithm).
No routine postprandial correction.
Rescue correction: ≥3h post-bolus + POC/CGM ≥300 mg/dL sustained.
CareSens Air (i-SENS, South Korea), 15-day sensor attached Day 0. 5-minute interval glucose transmitted to smartphone and Sens365 platform for research team monitoring.
Arm A: real-time CGM integrated into CareLevo bolus calculator.
Primary endpoint (24h TAR) and key secondary endpoint (window TAR 10:00-22:00) computed from Sens365 raw export.
15-day sensor covers entire study period (Day 1-14) without sensor change.
Provided free by manufacturer (i-SENS); manufacturer has no role in study design, analysis, or publication.
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Aktivní komparátor: Lantus-based MDI (Arm B)
Participants receive Lantus (insulin glargine U-100) once daily in the morning (45% of study TDD) with steroid.
Fiasp prandial bolus via insulin pen using a pre-printed dose table based on the same carbohydrate-band algorithm as Arm A. Correction via the same fixed printed table.
Insulin tapered from Day 10 proportionally to steroid taper.
|
Fiasp used as prandial and correction insulin in both arms.
Meal bolus via carbohydrate-band selection (0/30/45/60/75/90g).
ICR: breakfast 45g/(0.15×TDD);
lunch/dinner 60g/(0.20×TDD).
ISF = 1500/TDD (daytime), 2×ISF (night).
Arm A: app auto-calculation with IOB.
Arm B: pre-printed dose table (same algorithm).
No routine postprandial correction.
Rescue correction: ≥3h post-bolus + POC/CGM ≥300 mg/dL sustained.
CareSens Air (i-SENS, South Korea), 15-day sensor attached Day 0. 5-minute interval glucose transmitted to smartphone and Sens365 platform for research team monitoring.
Arm A: real-time CGM integrated into CareLevo bolus calculator.
Primary endpoint (24h TAR) and key secondary endpoint (window TAR 10:00-22:00) computed from Sens365 raw export.
15-day sensor covers entire study period (Day 1-14) without sensor change.
Provided free by manufacturer (i-SENS); manufacturer has no role in study design, analysis, or publication.
Lantus administered subcutaneously once daily in the morning with steroid intake.
Dose = 45% of study TDD.
De-escalated proportionally: Day 10-11 ×0.67, Day 12-13 ×0.33, Day 14 ×0.17 or discontinuation.
Selected over NPH for practical utility and supply stability; evidence supports comparable efficacy to NPH for GIH in BBI framework (Ruiz de Adana et al. 2018).
Toujeo/Tresiba excluded due to prolonged time to steady-state (≥5 days) incompatible with 14-day protocol.
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
24-hour CGM Time Above Range (TAR) >180 mg/dL (%) - averaged over Day 1-9
Časové okno: Day 1 through Day 9 (24 hours per day)
|
Percentage of CGM readings exceeding 180 mg/dL over 24 hours, averaged across the 9-day high-dose corticosteroid period (Day 1-9).
Calculated from 5-minute interval CareSens Air CGM raw data exported from Sens365 platform.
24-hour TAR is the standard CGM metric per international consensus guidelines and AGP reporting framework, enabling direct comparison with published literature on glucocorticoid-induced hyperglycemia.
Minimum 70% CGM data completeness per day required for inclusion in primary analysis; days with <70% completeness handled by multiple imputation in primary analysis and complete-case analysis as sensitivity analysis.
|
Day 1 through Day 9 (24 hours per day)
|
Sekundární výstupní opatření
Měření výsledku |
Časové okno |
|---|---|
|
CGM TAR >180 mg/dL (%) during steroid pharmacodynamic window (10:00-22:00) - pre-specified exploratory analysis of the steroid-specific time period corresponding to peak methylprednisolone effect
Časové okno: Day 1-9, 10:00-22:00 window
|
Day 1-9, 10:00-22:00 window
|
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Time In Range (TIR) 70-180 mg/dL (%, 24-hour)
Časové okno: Day 1-9
|
Day 1-9
|
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Time Above Range >250 mg/dL (%, 24-hour)
Časové okno: Day 1-9
|
Day 1-9
|
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Postprandial incremental AUC >180 mg/dL (breakfast, lunch, dinner - 2-4h post-meal)
Časové okno: Day 1-9
|
Day 1-9
|
|
Time Below Range (TBR) <70 mg/dL (%, 24-hour) - key safety outcome to verify TAR reduction is not accompanied by increased hypoglycemia
Časové okno: Day 1-9
|
Day 1-9
|
|
Nocturnal Time Below Range <70 mg/dL (00:00-06:00)
Časové okno: Day 1-9
|
Day 1-9
|
|
Severe hypoglycemia rate (requiring third-party assistance)
Časové okno: Day 1-14
|
Day 1-14
|
|
Glycemic variability: Coefficient of Variation (CV%), SD, MAGE
Časové okno: Day 1-9
|
Day 1-9
|
|
Number of daily needle punctures (bolus + correction injections/activations) - key treatment burden metric
Časové okno: Day 1-14
|
Day 1-14
|
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Total daily insulin dose and correction insulin proportion
Časové okno: Day 1-9
|
Day 1-9
|
|
Rate of rescue therapy (protocol stop criteria reached)
Časové okno: Day 1-14
|
Day 1-14
|
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CGM TAR >180 mg/dL and TBR <70 mg/dL during steroid taper period (Day 10-14) - exploratory safety
Časové okno: Day 10-14
|
Day 10-14
|
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Hearing recovery: PTA change (4-frequency average 0.5/1/2/4 kHz)
Časové okno: Baseline and Day 60 (±14 days)
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Baseline and Day 60 (±14 days)
|
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Hearing recovery: Siegel criteria classification (Complete/Partial/Minimal/No Recovery)
Časové okno: Day 60 (±14 days)
|
Day 60 (±14 days)
|
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Salvage intratympanic steroid injection rate
Časové okno: Day 60 (±14 days)
|
Day 60 (±14 days)
|
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Treatment satisfaction and device burden: ITSQ Inconvenience of Regimen subscale (Q1-Q5) and Insulin Delivery Device Satisfaction subscale (Q17-Q22); Anderson et al. Clin Ther 2004. Permission obtained.
Časové okno: Day 10-15 (outpatient visit)
|
Day 10-15 (outpatient visit)
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CGM data completeness and device-related events (patch premature removal, occlusion - Arm A)
Časové okno: Day 1-14
|
Day 1-14
|
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Treatment-related cost (CGM, insulin, device consumables)
Časové okno: Day 1-15
|
Day 1-15
|
Spolupracovníci a vyšetřovatelé
Sponzor
Publikace a užitečné odkazy
Obecné publikace
- American Diabetes Association Professional Practice Committee for Diabetes*. 16. Diabetes Care in the Hospital: Standards of Care in Diabetes-2026. Diabetes Care. 2026 Jan 1;49(Supplement_1):S339-S355. doi: 10.2337/dc26-S016.
- Chang LL, Umpierrez GE, Inzucchi SE. Management of Hyperglycemia in Hospitalized, Non-Critically Ill Adults. N Engl J Med. 2022 Sep 15;387(11):1040-1042. doi: 10.1056/NEJMclde2204691. No abstract available.
- Anderson RT, Skovlund SE, Marrero D, Levine DW, Meadows K, Brod M, Balkrishnan R. Development and validation of the insulin treatment satisfaction questionnaire. Clin Ther. 2004 Apr;26(4):565-78. doi: 10.1016/s0149-2918(04)90059-8.
- Cho JH, Suh S. Glucocorticoid-Induced Hyperglycemia: A Neglected Problem. Endocrinol Metab (Seoul). 2024 Apr;39(2):222-238. doi: 10.3803/EnM.2024.1951. Epub 2024 Mar 27.
- Chandrasekhar SS, Tsai Do BS, Schwartz SR, Bontempo LJ, Faucett EA, Finestone SA, Hollingsworth DB, Kelley DM, Kmucha ST, Moonis G, Poling GL, Roberts JK, Stachler RJ, Zeitler DM, Corrigan MD, Nnacheta LC, Satterfield L. Clinical Practice Guideline: Sudden Hearing Loss (Update). Otolaryngol Head Neck Surg. 2019 Aug;161(1_suppl):S1-S45. doi: 10.1177/0194599819859885.
- Kleinhans M, Albrecht LJ, Benson S, Fuhrer D, Dissemond J, Tan S. Continuous Glucose Monitoring of Steroid-Induced Hyperglycemia in Patients With Dermatologic Diseases. J Diabetes Sci Technol. 2024 Jul;18(4):904-910. doi: 10.1177/19322968221147937. Epub 2023 Jan 5.
- Achanta M, Kasetti P, Fortune-Ely M, Ross T, Magos T, Manjaly JG. Adverse Effects of Steroid Therapy in Sudden Sensorineural Hearing Loss: A Scoping Review. Clin Otolaryngol. 2025 Sep;50(5):821-830. doi: 10.1111/coa.14339. Epub 2025 May 30.
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Odhadovaný)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Neurologické projevy
- Onemocnění endokrinního systému
- Nemoci nervového systému
- Metabolické choroby
- Poruchy metabolismu glukózy
- Diabetes Mellitus
- Otorinolaryngologická onemocnění
- Poruchy vnímání
- Nemoci uší
- Ztráta sluchu
- Poruchy sluchu
- Patologické stavy, příznaky a symptomy
- Nutriční a metabolické nemoci
- Příznaky a symptomy
- Diabetes mellitus, typ 2
- Prediabetický stav
- Ztráta sluchu, náhlá
- Hormony
- Hormony, hormonální náhražky a antagonisté hormonů
- Peptidové hormony
- Peptidy
- Aminokyseliny, peptidy a proteiny
- Inzulín, dlouhodobě
- Inzulíny
- Pankreatické hormony
- Inzulín, krátkodobý
- Inzulin glargin
- Inzulin Aspart
Další identifikační čísla studie
- HDSH-ENDO-2026-SHIP-001
Plán pro data jednotlivých účastníků (IPD)
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Popis plánu IPD
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
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Klinické studie na CareLevo Patch-type Insulin Pump
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