Repurposing Insulin With Intranasal Administration to Improve Function After Mild Traumatic Brain Injury (INI TBI)

This Phase II clinical trial protocol will provide evidence as to whether IN insulin is efficacious in reducing symptoms in people seeking care for mild TBI (concussion).

Study Overview

• Status: Recruiting
• Conditions: Mild Traumatic Brain Injury; Concussion (Diagnosis)
• Intervention / Treatment: Drug: Insulin (Humulin); Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 96
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Research Coordinator; Phone Number: 651-495-6363; Email: ClinicalTrials@HealthPartners.com

Study Locations

• United States
  • Minnesota
    • Saint Paul, Minnesota, United States, 55130
      • Recruiting
      • HealthPartners Neuroscience Center
      • Contact: Clinical Trial Coordinator; Phone Number: 651-495-6360; Email: ClinicalTrials@HealthPartners.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject has presented to a clinic/ER reporting an acute head injury (e.g., a closed head injury or blunt TBI) and presents with at least two symptoms of TBI, as defined by the listed symptoms on the Post-Concussion Symptom Scale (PCSS)
• Subject is considered high risk for persistent post-concussion symptoms using the post-concussion symptom (PoCS) clinical decision rule
• Subject is between ≥18 and ≤65 years of age
• Treatment can be initiated within 5-14 days after injury, inclusive
• Subject must be proficient in speaking English in order to comply with instructions and measures for the study
• Subject must be able to consent
• Female subjects of childbearing potential must have a negative pregnancy test at the baseline visit and be willing to use a medically acceptable contraceptive method for the duration of the study

Exclusion Criteria:

• Subject's concussion or TBI resulted in loss of consciousness of > 30 minutes
• Subject has evidence of acute intracranial hemorrhage at screening
• Subjects has received an intranasal vaccine within 2 weeks of the date of their baseline visit
• Subject has medical history and/or clinically determined disorders: chronic sinusitis, previous nasal and/or oto-pharyngeal surgery, and severe deviated septum and/or other anomalies, including findings of an abnormal nasopharyngeal exam that could interfere with intranasal administration as judged by the PI, e.g., inflammation, erythema, bleeding, atrophy, septal perforation, mucosal erosion, localized infection or ulceration, polyposis.
• Subject has history of any of the following: active and significant central nervous system, psychiatric illness, pulmonary, or cardiovascular disorders or any other clinically relevant abnormality that inclusion would pose a safety risk to the subject as determined by investigator
• Subject has evidence of blast injury, electrocution injury, or significant multisystem trauma associated with the mTBI, including significant nasal trauma
• Subject has participated in a clinical trial investigation (drug or device) within 3 months of this study.
• Subject has an insulin allergy
• Subject is taking insulin for Type I or Type II diabetes
• Subject is pregnant or breast feeding
• Subjects with nasal piercings or any physical finding in the nose that, in the opinion of the PI, would be likely to interfere with successful completion of dosing

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose 1 - 40 IU/IN (20 IU, twice daily x 21 days); Intranasal insulin, lower dose, 40 IU insulin, twice daily for 21 days	Drug: Insulin (Humulin); Intranasal regular insulin
Experimental: Dose 2 - 80 IU/IN (40 IU, twice daily x 21 days); Intranasal insulin, higher dose, 80 IU insulin, twice daily for 21 days	Drug: Insulin (Humulin); Intranasal regular insulin
Placebo Comparator: Dose 3 - Placebo; intranasal, twice daily for 21 days	Drug: Placebo; Intranasal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Post-Concussion Symptom Scale scores (PCSS) from baseline to 21 days	The PCSS is a 22-item self-report inventory of concussion symptoms. Each symptom is rated for severity from 0 (none) to 6 (severe), giving a total score of 0 to 132; higher scores indicate greater symptom burden. Change is calculated as the Day 21 score minus the baseline score, so negative values indicate improvement. Each insulin arm (40 IU and 80 IU) is compared separately with saline, and results are reported as the difference in mean change (insulin minus saline) with a 97.5% confidence interval.	baseline and day 21 post-intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in time to return to normal activities by day 21	Number of days from intervention to participant-reported return to normal activities. Participants who have not reported a return to normal activities by Day 21 are censored at their last observation. Each insulin arm (40 IU and 80 IU) is compared separately with saline, and results are reported as a hazard ratio (insulin vs. saline) with a 95% confidence interval; a hazard ratio greater than 1 indicates faster return to normal activities with insulin.	baseline and day 21 post-intervention
Change in Quality of Life after Brain Injury (QOLIBRI) scores from baseline to 21 days	The QOLIBRI is a 37-item self-report measure of health-related quality of life after traumatic brain injury. The total score ranges from 0 to 100; higher scores indicate better quality of life. Change is calculated as the Day 21 score minus the baseline score, so positive values indicate improvement. Each insulin arm (40 IU and 80 IU) is compared separately with saline, and results are reported as the difference in mean change (insulin minus saline) with a 95% confidence interval.	baseline and day 21 post-intervention

Collaborators and Investigators

• Sponsor: HealthPartners Institute
• Investigators: Principal Investigator: Bhavani Kashyap, MBBS, PhD, HealthPartners Institute Neuroscience Research

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: November 9, 2026
• First Submitted That Met QC Criteria: November 9, 2026
• First Posted (Actual): November 13, 2026

Study Record Updates

• Last Update Posted (Actual): November 13, 2026
• Last Update Submitted That Met QC Criteria: November 9, 2026
• Last Verified: November 1, 2026

More Information

Terms related to this study

• Keywords: intranasal; insulin
• Additional Relevant MeSH Terms: Brain Injuries, Traumatic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Pathologic Processes; Metabolic Diseases; Glucose Metabolism Disorders; Hyperinsulinism; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds, Nonpenetrating; Brain Injuries; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Disease; Brain Concussion; Insulin Resistance; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins; Insulins; Pancreatic Hormones; Proinsulin; Insulin
• Other Study ID Numbers: A25-357

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No