NCT04251585: INI-PD

Intranasal Insulin in Parkinson's Disease

Completed Phase 2 Results posted Last updated 11 February 2026

What this trial tests

Phase 2 trial testing Regular Novolin R in Parkinson Disease in 31 participants. Completed in 27 August 2024.

Timeline

4 February 2020

Primary endpoint
27 August 2024

27 August 2024

Quick facts

Lead sponsor	HealthPartners Institute
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	other
Enrollment	31
Start date	4 February 2020
Primary completion	27 August 2024
Estimated completion	27 August 2024
Sites	1 location across United States

Drugs / interventions tested

• Regular Novolin R — full drug profile →
• Placebo

Conditions studied

• Parkinson Disease — all drugs for Parkinson Disease →

Sponsor

HealthPartners Institute

Who can join

Adults 41 to 89, any sex, with Parkinson Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Safety Measured by Count of Safety Events Primary · 3 weeks

Composite safety event - this is a count of either a reduction of fasting glucose to \<70 mg/dL or an unintended reduction of weight \>5%. A larger composite event count indicates a less safe treatment.

Group	Value	95% CI
Low Insulin	0
Medium Insulin	0
High Insulin	0
Placebo	0

Safety Measured by Fasting Glucose Primary · baseline and 3 weeks

Pre-post change in fasting glucose (mg/dL). A larger decrease in fasting glucose indicates a less safe treatment.

Group	Value	95% CI
Low Insulin	-3.8	-6.9 – -1.0
Medium Insulin	-1.3	-6.8 – 4.2
High Insulin	-5.9	-10 – -1.8
Placebo	-3.8	-9.8 – 2.1

Safety Measured by Body Weight Primary · baseline and 3 weeks

Pre-post change in body weight (lbs). An unintended decrease in body weight indicates a less safe treatment.

Group	Value	95% CI
Low Insulin	-0.63	-1.8 – 0.50
Medium Insulin	0.34	-1.6 – 2.3
High Insulin	-0.33	-1.9 – 1.3
Placebo	-0.55	-3.0 – 1.9

Safety Measured by the Number of Serious Adverse Events (SAE) and Adverse Events (AE) Primary · 3 weeks

Total number of AEs/SAEs during the course of treatment. More AEs/SAEs indicates a less safe treatment.

SAE

Group	Value	95% CI
Low Insulin	0	± 0
Medium Insulin	0	± 0
High Insulin	0	± 0
Placebo	0	± 0

AE

Group	Value	95% CI
Low Insulin	2.8	± 1.2
Medium Insulin	5.0	± 2.8
High Insulin	2.0	± 3.8
Placebo	3.0	± 0.89

Cognitive Function Measured by the Montreal Cognitive Assessment (MoCA) Secondary · 5 weeks

Pre-post difference. Total sum of scores. Range: 0-30. Higher score indicates less memory loss

Group	Value	95% CI
Low Insulin	-1.0	-3.0 – 1.0
Medium Insulin	-0.71	-2.5 – 1.1
High Insulin	0.67	-0.93 – 2.3
Placebo	0.5	-1.5 – 2.5

Cognitive Function Measured by the Weschler Adult Intelligence Scale - Fourth Edition (WAIS-IV) Digit Span Secondary · 3 weeks

Pre-post difference. Scaled score. Range: 1-19. Forward and backward. Lower score indicates more impairment.

Forward Digit Span

Group	Value	95% CI
Low Insulin	1.5	-0.33 – 3.3
Medium Insulin	1.0	-0.69 – 2.7
High Insulin	0.2	-1.3 – 1.7
Placebo	1.0	-0.83 – 2.8

Backward Digit Span

Group	Value	95% CI
Low Insulin	0.0	-2.0 – 2.0
Medium Insulin	-0.43	-2.3 – 1.5
High Insulin	0.0	-1.7 – 1.7
Placebo	2.3	0.29 – 4.4

Cognitive Function Measured by the Trailmaking Test Part A Time Secondary · baseline and 3 weeks

Pre-post difference. T-score. Mean: 50, Standard deviation: 10. A higher T-score indicates a better outcome/performance. Clinically, 1-1.5 standard deviations would be significant, 2 standard deviations would be considered abnormal/impaired.

Group	Value	95% CI
Low Insulin	4.5	-3.3 – 12.3
Medium Insulin	5.3	-1.9 – 12.5
High Insulin	4.7	-1.6 – 11.1
Placebo	5.8	-1.9 – 13.6

Cognitive Function Measured by the Trailmaking Test Part B Time Secondary · baseline and 3 weeks

Pre-post difference. T-score. Mean: 50, Standard deviation: 10. A higher T-score indicates a better outcome/performance. Clinically, 1-1.5 standard deviations would be significant, 2 standard deviations would be considered abnormal/impaired.

Group	Value	95% CI
Low Insulin	3.5	-3 – 10
Medium Insulin	5.6	-0.43 – 11.6
High Insulin	2.1	-3.2 – 7.4
Placebo	-2.8	-9.3 – 3.7

Cognitive Function Measured by the Trailmaking Test Parts A & B Errors Secondary · 3 weeks

Pre-post difference. Total number of errors. No range. More errors indicate more impairment.

Group	Value	95% CI
Low Insulin	0	-1.8 – 7.8
Medium Insulin	0	-0.53 – 0.53
High Insulin	-0.56	-1.5 – 0.40
Placebo	0	-0.66 – 0.66

Cognitive Function Measured by the Judgement of Line Orientation Secondary · baseline and 3 weeks

Judgement of Line Orientation is an assessment of visuospatial ability. A Z-score of 0 represents the population mean. Pre-post difference. A positive difference indicates an improvement.

Group	Value	95% CI
Low Insulin	0.06	-0.64 – 0.70
Medium Insulin	0.19	-0.38 – 0.77
High Insulin	-0.44	-0.94 – 0.07
Placebo	0.21	-0.41 – 0.84

Cognitive Function Measured by the Logical Memory Scaled Scores Secondary · baseline and 3 weeks

Pre-post difference. Scaled score. Range: 1-19. Logical memory immediate and delayed. Lower score indicates more impairment.

Immediate Recall

Group	Value	95% CI
Low Insulin	2.7	0.23 – 5.1
Medium Insulin	2.4	0.17 – 4.7
High Insulin	1.3	-0.66 – 3.3
Placebo	3.5	1.1 – 5.9

Delayed Recall

Group	Value	95% CI
Low Insulin	1.7	-0.15 – 3.5
Medium Insulin	4.0	2.3 – 5.7
High Insulin	2.4	0.96 – 3.7
Placebo	2.5	-0.69 – 4.3

Cognitive Function Measured by the Logical Memory, Recognition Secondary · baseline and 3 weeks

Pre-post difference in median category from baseline to 3 weeks on the Logical memory, recognition subscale. Scoring of this and all outcomes were based on best practices conveyed by study neuropsychologist during study design, and scoring approaches were chosen completely a priori. The recognition outcome of the LM test is derived from a series of conversions, as follows. First, the raw "process" score is converted to cumulative percentage (0-100). Because the cumulative percentage distribution is known to be skewed, best practice is to report scores as the following ordinal categorizations o

Group	Value	95% CI
Low Insulin	1	0 – 5
Medium Insulin	0	0 – 2
High Insulin	0	-1 – 2
Placebo	1	-1 – 3

Adverse events — posted to ClinicalTrials.gov

Time frame: 5 weeks. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Low Insulin

Serious: 0/6 (0%)

Deaths: 0/6

Medium Insulin

Serious: 0/7 (0%)

Deaths: 0/7

High Insulin

Serious: 0/9 (0%)

Deaths: 0/9

Placebo

Serious: 0/6 (0%)

Deaths: 0/6

Other adverse events (10 terms — click to expand)

Reaction	System	Low Insulin	Medium Insulin	High Insulin	Placebo
Nasal irritation	Skin and subcutaneous tissue disorders	—	—	—	—
Nose bleeds	General disorders	—	—	—	—
Other	General disorders	—	—	—	—
Respiratory/sinus symptoms	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Increased blood pressure	Blood and lymphatic system disorders	—	—	—	—
Headache	General disorders	—	—	—	—
Gastrointestinal issues	Gastrointestinal disorders	—	—	—	—
Muscle aches, pains, and sprains	Musculoskeletal and connective tissue disorders	—	—	—	—
Falls	Ear and labyrinth disorders	—	—	—	—
Light-headedness, dizzyness	General disorders	—	—	—	—

Data from ClinicalTrials.gov NCT04251585 adverse events section.

Sponsor's own description

This project will investigate exploratory outcomes related to the effect of intranasal insulin on cognition, mood, apathy and motor performance of subjects with Parkinson's disease over a 3 week period.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Recent Advances in Intranasal Administration for Brain-Targeting Delivery: A Comprehensive Review of Lipid-Based Nanoparticles and Stimuli-Responsive Gel Formulations.
   Koo J, Lim C, Oh KT. · · 2024 · cited 57× · PMID 38414526 · DOI 10.2147/ijn.s439181
2. Parkinson's Disease Drug Therapies in the Clinical Trial Pipeline: 2021 Update.
   McFarthing K, Rafaloff G, Baptista MAS, Wyse RK, et al · · 2021 · cited 46× · PMID 34151864 · DOI 10.3233/jpd-219006
3. Nose-to-brain drug delivery: from bench to bedside.
   Drath I, Richter F, Feja M. · · 2025 · cited 23× · PMID 40390100 · DOI 10.1186/s40035-025-00481-w
4. Parkinson's disease therapy: what lies ahead?
   Wolff A, Schumacher NU, Pürner D, Machetanz G, et al · · 2023 · cited 19× · PMID 37147404 · DOI 10.1007/s00702-023-02641-6
5. The Nasal-Brain Drug Delivery Route: Mechanisms and Applications to Central Nervous System Diseases.
   Qiu Y, Huang S, Peng L, Yang L, et al · · 2025 · cited 18× · PMID 40487748 · DOI 10.1002/mco2.70213
6. Metabolomics as a Crucial Tool to Develop New Therapeutic Strategies for Neurodegenerative Diseases.
   Lanznaster D, Dingeo G, Samey RA, Emond P, et al · · 2022 · cited 7× · PMID 36144268 · DOI 10.3390/metabo12090864
7. Restoring autophagic function: a case for type 2 diabetes mellitus drug repurposing in Parkinson's disease.
   Greco M, Munir A, Musarò D, Coppola C, et al · · 2023 · cited 5× · PMID 38027497 · DOI 10.3389/fnins.2023.1244022
8. High-dose intranasal insulin in an adaptive dose-escalation study in healthy human participants.
   Schmitzberger F, Fowler J, Hsu CH, Pai MP, et al · · 2024 · cited 1× · PMID 39558506 · DOI 10.1111/cts.70071