Intranasal Insulin to Prevent Intensive Care Unit Delirium (INSPIRE)

Intranasal Insulin for the Prevention of Delirium in ICU Patients Undergoing Elective Cardiac Surgery: a Randomized, Double-blind, Placebo-controlled Pilot Trial (INSPIRE)

This study aims to assess the feasibility, tolerability, and exploratory efficacy of intranasal insulin to prevent delirium in ICU patients aged ≥65 years after complex elective cardiac surgery with cardiopulmonary bypass

Study Overview

• Status: Not yet recruiting
• Conditions: Delirium - Postoperative
• Intervention / Treatment: Drug: Intranasal insulin-40U; Drug: Intranasal sodium chloride 0.9%

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Rens Kooken, MD; Phone Number: +3124361673; Email: rens.kooken@radboudumc.nl

Study Locations

• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525GA
      • Radboud University Medical Center
      • Contact: Rens Kooken, MD; Phone Number: +3124361673; Email: rens.kooken@radboudumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥65 years
2. Planned surgical admission to the ICU of the Radboudumc following complex cardiac surgery with CPB. Complex cardiac surgery is defined as all cardiac on-pump procedures except for isolated CABG
3. Able to receive intranasal spray (no obstructive nasal pathology precluding administration)
4. Informed consent from patient

Exclusion Criteria:

1. Delirium at hospital admission
2. Non-complex or off-pump cardiac surgery
3. Known allergy/hypersensitivity to insulin or formulation excipients
4. Contra-indication for nasal administration (severe nasal pathology, recent nasal/sinus surgery, active epistaxis, active rhinitis, obstruction of either one or both nostrils)
5. Participating in other investigational medication trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intranasal insulin; Intranasal insulin administered twice daily. Each administration consists of two sprays of 10 IU (0.1 ml) in alternating nostrils, totalling to 40 IU per day.	Drug: Intranasal insulin-40U; Intranasal isophane insulin administered twice daily. Each administration consists of two sprays of 10 IU (0.1 ml) in alternating nostrils, totalling to 40 IU per day.
Placebo Comparator: Intranasal placebo (NaCl 0.9%); Intranasal placebo (sodium chloride 0.9%) administered twice daily. Each administration consists of two sprays of 0.1 ml in alternating nostrils, totalling to 0.4 mL per day.	Drug: Intranasal sodium chloride 0.9%; Intranasal sodium chloride 0.9% administered twice daily. Each administration consists of two sprays of 0.1 ml in alternating nostrils, totalling to 0.4mL per day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility: rate of recruitment	Proportion of eligible patients who are enrolled and randomized during the recruitment period.	From start of study to end of study, with a maximum of 12 months
Feasibility: protocol adherence	Number of administered doses divided by number of planned doses	From start of treatment up to a maximum of 5 days
Feasibility: participant retention and follow-up completeness	Proportion of randomized participants completing in-hospital data collection and 30-day follow-up (TICS-m).	From start of study to end of study, with a maximum of 12 months
Tolerability	- Local nasal adverse events (e.g., irritation, epistaxis) and incidence of hypoglycaemia (mild: glucose <4.1 mmol/L, severe: <2.2 mmol/L), defined as the number of local nasal adverse events and hypoglycaemia events.	From start of treatment up to a maximum of 5 days
Exploratory efficacy	Delirium severity as assessed with the Delirium Rating Scale-Revised-98 (DRS-R-98)	From start of treatment up to a maximum of 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delirium incidence	Defined as >= 1 positive delirium assessment(s)	From start of treatment up to a maximum of 7 days
Delirium severity	Numeric, as assessed with the Delirium Rating Scale-Revised-98 (DRS-R-98)	From start of treatment up to a maximum of 7 days
Delirium duration	Defined as number of days with positive delirium assessment	From start of treatment up to a maximum of 7 days
Delirium and coma-free days	Defined as the number of days without delirium or coma	From start of treatment up to a maximum of 7 days
Exposure to antipsychotics, sedatives and benzodiazepines	Defined as the number of patients receiving antipsychotics, sedatives, or benzodiazepines	From start of treatment up to a maximum of 7 days
Length of ICU stay	Defined as days spent in the ICU	From ICU admission to ICU discharge, assessed up to 6 months
Length of hospital stay	Defined as days spent in the hospital	From hospital admission to discharge, assessed up to 6 months
Change in cognitive function	Assessed with the modified Telephone Interview for Cognitive Status (TICS-m) at baseline (before hospital admission) and 30 days after surgery	From informed consent to 30 days post-surgery

Collaborators and Investigators

• Sponsor: Radboud University Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): April 15, 2026
• Primary Completion (Estimated): July 15, 2026
• Study Completion (Estimated): August 15, 2026

Study Registration Dates

• First Submitted: April 2, 2026
• First Submitted That Met QC Criteria: April 9, 2026
• First Posted (Actual): April 16, 2026

Study Record Updates

• Last Update Posted (Actual): April 16, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Postoperative Complications; Pathologic Processes; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Emergence Delirium
• Other Study ID Numbers: 2025-524680-21-00

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Upon reasonable request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No