The NOSE-PD trial (NCT05266417) is a Phase 2 randomized, double-blind, placebo-controlled study evaluating the safety, tolerability, and efficacy of intranasal insulin and glutathione (INS-GSH) as an add-on therapy for patients with Parkinson's Disease[1]. This trial represents a novel approach targeting both insulin signaling dysfunction and oxidative stress — two key mechanisms implicated in dopaminergic neuron degeneration.
The study is sponsored by the Gateway Institute for Brain Research and is currently recruiting participants at sites in Florida.
| Attribute | Value |
|---|---|
| NCT Number | NCT05266417 |
| Official Title | A Randomized, Double-Blind, Placebo-Controlled, Phase II Study to Evaluate the Safety, Tolerability, and Efficacy of Intranasal Insulin and Glutathione as an Add-On Therapy in Subjects With Parkinson's Disease (NOSE-PD) |
| Phase | Phase 2 |
| Status | Recruiting |
| Enrollment | 56 participants (estimated) |
| Start Date | February 7, 2022 |
| Primary Completion | December 2026 |
| Completion | January 2027 |
| Sponsor | Gateway Institute for Brain Research |
| Design | Randomized, Triple-Blind, Placebo-Controlled, Parallel Assignment |
| Arm | Type | Intervention |
|---|---|---|
| Active | Experimental | Intranasal Insulin (Novolin R) and Glutathione (INS-GSH) twice daily |
| Control | Placebo Comparator | Intranasal matched placebos (insulin placebo + glutathione placebo) twice daily |
Institute for Neuroimmune Medicine — Davie, Florida, 33314
Las Mercedes Medical Research — Hialeah, Florida, 33012
This trial targets two complementary pathological pathways in Parkinson's disease:
Insulin signaling dysfunction in the brain is increasingly recognized as a key contributor to neurodegeneration — a concept formalized as Type 3 Diabetes[2]. In PD, brain insulin resistance contributes to:
The intranasal route bypasses the blood-brain barrier, delivering insulin directly to the brain via the olfactory and trigeminal pathways[3]. This approach avoids systemic hypoglycemia and peripheral insulin side effects while achieving therapeutic concentrations in the CNS.
Glutathione is the brain's primary endogenous antioxidant. PD patients show significantly reduced glutathione levels in the substantia nigra[4], making this a rational therapeutic target:
The combination of insulin and glutathione addresses both sides of the oxidative stress equation:
This dual approach may provide more comprehensive neuroprotection than targeting either pathway alone.
| Measure | Description | Timepoint |
|---|---|---|
| Verbal Fluency | F, A, and S (FAS) words test | 24 weeks |
| Measure | Description | Timepoint |
|---|---|---|
| Verbal Fluency | FAS test | 28 weeks |
| Motor Function | Timed Up and Go (TUG) test | 24 weeks |
| Motor Function | MDS-UPDRS Part III (motor examination) | 24 weeks |
| Motor Function | MDS-UPDRS total score | 24 weeks |
| Clinical Global Impression | CGI score | 24 weeks |
| Disease Severity | CISI-PD (Clinical Impression of Severity Index) | 24 weeks |
| Cognitive Function | Cambridge Brain Sciences computerized battery (12 tasks) | 24 weeks |
| Depression | Hamilton Rating Scale for Depression | 24 weeks |
| Quality of Life | PDQ-39 | 24 weeks |
| Patient Global Impression | PGI score | 24 weeks |
The insulin-IGF1 signaling pathway plays a critical role in neuronal survival. Multiple studies have demonstrated:
Post-mortem studies consistently show:
The intranasal drug delivery approach offers several advantages:
NCT05266417 — Intranasal Insulin and Glutathione as an Add-On Therapy in Parkinson's Disease. ↩︎
Type 3 Diabetes Hypothesis — Brain Insulin Resistance in Neurodegeneration. ↩︎
Intranasal Drug Delivery Mechanisms. ↩︎
Glutathione Metabolism in Neurodegeneration. ↩︎
Exenatide Parkinson's Disease Trial. ↩︎