Intranasal Insulin for Post-Traumatic Stress Disorder

Overseen By Gihyun Yoon, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: VA Connecticut Healthcare System

Must not be taking: Insulin, Psychotropics

Disqualifiers: Diabetes, Traumatic brain injury, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether intranasal insulin can help reduce symptoms of PTSD (post-traumatic stress disorder). Participants will receive either the insulin treatment or a placebo to determine any differences in symptom changes. This trial represents a step toward finding new ways to manage PTSD. It might suit individuals with PTSD who are not facing other major medical or mental health conditions. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to potentially groundbreaking PTSD treatment advancements.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop your current medications, but it does require that you haven't changed doses of psychotropic medications in the past 4 weeks. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies found that using insulin through a nasal spray is safe for people. Research shows that these trials did not report any serious safety issues. Specifically, participants experienced no major side effects or symptoms of low blood sugar. This suggests that insulin nasal spray is well-tolerated, making it a promising option for further research in treating conditions like PTSD. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for PTSD?

Most treatments for PTSD, such as therapy and medications like SSRIs, focus on managing symptoms over time. But intranasal insulin works differently by targeting brain function directly. This treatment is unique because it leverages insulin's role in brain signaling to potentially improve cognitive function and emotional regulation rapidly. The intranasal delivery method is particularly exciting as it allows insulin to reach the brain directly, bypassing the bloodstream, which may lead to faster and more targeted effects. Researchers are hopeful that this approach could offer a new, efficient way to alleviate PTSD symptoms.

What evidence suggests that intranasal insulin might be an effective treatment for PTSD?

Research has shown that using insulin through a nasal spray might help reduce PTSD symptoms. In this trial, some participants will receive intranasal insulin, which studies have found can lower feelings of anxiety and depression, especially when used soon after a traumatic event. It has also improved brain function and memory in other conditions, like Alzheimer's disease. These findings suggest it might help with PTSD by calming overactive brain areas, such as the amygdala, which is involved in stress responses. Early results are promising, but more research is needed to fully understand its benefits for PTSD. ^{1 2 6 7 8}

Who Is on the Research Team?

Gihyun Yoon, MD

Principal Investigator

VA Connecticut Healthcare System

Are You a Good Fit for This Trial?

This trial is for men and women aged 21-65 with current PTSD who can consent to participate. It's not for those with severe brain injuries, metal in their body that affects MRI, claustrophobia, recent changes in mental health treatments, unstable medical conditions, diabetes treated with insulin or pills, high suicide/homicide risk, contraindication to insulin use or certain psychiatric disorders.

Inclusion Criteria

Male or female, 21-65 years old

You currently have PTSD.

Able to provide written informed consent

Exclusion Criteria

You have a serious injury to your brain.

Presence of cardiac pacemaker or other electronic device or ferromagnetic metal foreign bodies in vulnerable positions as assessed by a standard pre-MRI safety screening questionnaire

You have a fear of enclosed spaces (claustrophobia).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 40 IU of intranasal insulin twice a day or placebo

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Intranasal Insulin
• Placebo

Trial Overview The study tests if intranasal insulin can help reduce symptoms of PTSD compared to a placebo (a substance with no active drug). Participants will receive either the nasal spray containing insulin or a placebo without knowing which one they are getting.

How Is the Trial Designed?

Group I: Placebo Experimental Treatment 1 Intervention

Subjects in this arm will receive placebo.

Group II: Intranasal insulin Experimental Treatment 1 Intervention

Subjects in this arm will receive 40 IU of intranasal insulin twice a day (80 IU per day).

Intranasal Insulin is already approved in United States, European Union for the following indications:

Approved in United States as Intranasal insulin for:

• Diabetes

Approved in European Union as Intranasal insulin for:

• Diabetes

Who Is Running the Clinical Trial?

VA Connecticut Healthcare System

Lead Sponsor

Trials

86

Recruited

8,800+

Published Research Related to This Trial

The study demonstrated that administering intranasal insulin in a single nostril significantly enhances absorption, achieving higher maximum concentrations (C(max)) compared to dual nostril administration, with maximum levels reaching 96 µU/ml for a 75 U dose.

The enhanced absorption was attributed to the increased amount of insulin administered rather than the absorption enhancer CPE-215, indicating that higher doses of insulin can improve its effectiveness when delivered intranasally.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced absorption of Nasulin™, an ultrarapid-acting intranasal insulin formulation, using single nostril administration in normal subjects. Stote, R., Miller, M., Marbury, T., et al.[2021]

Intranasal insulin administration significantly improved spatial learning and memory in a rat model of Alzheimer's disease, while intraperitoneal insulin did not show a notable effect.

The study used a rat model with amyloid-beta infusion to simulate Alzheimer's, and the effects were assessed over 14 days using the Morris water maze test, highlighting the potential of intranasal insulin as a non-invasive treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intranasal insulin treatment improves memory and learning in a rat amyloid-beta model of Alzheimer's disease. Farzampour, S., Majdi, A., Sadigh-Eteghad, S.[2019]

A review of 38 studies involving 1092 individuals found that intranasal human insulin is generally safe, with no reports of severe adverse events or symptomatic hypoglycemia, although some participants experienced transient nasal irritation.

The studies indicated that while intranasal insulin has a chemical stability of up to 57 days, there is insufficient data on the long-term safety of chronic use, highlighting the need for improved formulations to reduce nasal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of intranasal human insulin: A review. Schmid, V., Kullmann, S., Gfrörer, W., et al.[2018]

In a study involving 17 subjects with non-insulin dependent diabetes mellitus (NIDDM), nasally administered insulin significantly reduced post-meal blood sugar levels, with the most effective regimen achieving a 70% reduction in glucose levels over 240 minutes.

The nasal insulin was well-tolerated, with no cases of symptomatic hypoglycemia reported and only minor nasal irritation observed in a few instances, indicating it is a safe alternative for managing postprandial glucose levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intranasal insulin: the effects of three dose regimens on postprandial glycaemic profiles in type II diabetic subjects. Coates, PA., Ismail, IS., Luzio, SD., et al.[2019]

Intranasal administration of insulin is a promising alternative to traditional injections, offering easier administration and better patient acceptance.

The review discusses various factors that can affect insulin absorption through the nasal route, including anatomical and physiological considerations, as well as the use of absorption promoters in clinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intranasal administration of insulin to humans. Gizurarson, S., Bechgaard, E.[2019]

The intranasal insulin formulation (Nasulin) was well tolerated in a study of 13 healthy male volunteers, showing a significant rise in serum insulin and a decrease in plasma glucose after administration.

Nasulin demonstrated a peak insulin absorption time of 10-20 minutes, with a relative absorption of 12.0% from the dominant nostril and 15.4% from the nondominant nostril, indicating it can be effectively administered regardless of nasal cycle.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of intranasal insulin spray (Nasulin) administered to healthy male volunteers: infuence of the nasal cycle. Leary, AC., Dowling, M., Cussen, K., et al.[2021]

Intranasal insulin administration effectively targets insulin signaling in the brain while minimizing systemic side effects, making it a promising method for enhancing cognitive function and metabolic control.

Research indicates that improving brain insulin signaling could be a potential therapy for neurodegenerative diseases linked to metabolic disorders, highlighting the importance of addressing brain insulin resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes and clinical implications of intranasal insulin administration to the central nervous system. Santiago, JCP., Hallschmid, M.[2020]

Intranasal insulin (INI) has been shown to improve global cognition in patients with Alzheimer's disease and mild cognitive impairment, based on a meta-analysis of 29 studies involving 1,726 participants.

However, INI did not demonstrate significant cognitive benefits in healthy individuals or other patient populations, indicating that its effects may be specific to certain cognitive disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes and clinical implications of intranasal insulin on cognition in humans: A systematic review and meta-analysis. Wu, S., Stogios, N., Hahn, M., et al.[2023]

In a trial involving 60 adults with mild cognitive impairment (MCI) or Alzheimer's disease (AD), intranasal insulin detemir at a dose of 40 IU showed significant improvements in memory and working memory compared to placebo, particularly benefiting APOE-ε4 carriers.

The study found that higher baseline insulin resistance predicted greater cognitive improvement with the 40 IU dose, but no significant effects were observed on daily functioning or executive functioning, indicating a specific impact on cognitive aspects rather than overall daily activities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting intranasal insulin detemir improves cognition for adults with mild cognitive impairment or early-stage Alzheimer's disease dementia. Claxton, A., Baker, LD., Hanson, A., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04044534

Intranasal Insulin for Posttraumatic Stress Disorder The current proposal aims to study the pharmacotherapeutic effects of intranasal insulin on PTSD symptoms and inhibition of amygdala hyperactivation in ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022395625004455

Intranasal insulin administration improves anxiety These findings suggest that intranasal administration of insulin early after trauma could lead to anxiolytic and antidepressant effects through ...

3. withpower.com withpower.com/trial/phase-3-stress-disorders-post-traumatic-7-2021-d6d80

Intranasal Insulin for Post-Traumatic Stress Disorder Research shows that intranasal insulin can improve brain function and memory in conditions like Alzheimer's disease and mild cognitive impairment, suggesting it ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04044534?term=Intranasal&aggFilters=status:not%20rec%20enr%20act&viewType=Table&rank=9

Intranasal Insulin for Posttraumatic Stress Disorder | ... Study Overview. Brief Summary. To evaluate if intranasal insulin is effective in reducing PTSD symptoms. Detailed Description.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40763642/

and depressive-like behaviors in PTSD-exposed rats These findings suggest that intranasal administration of insulin early after trauma could lead to anxiolytic and antidepressant effects ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7007475/

Intranasal Insulin: a Treatment Strategy for Addiction - PMC A recent review of safety of intranasal human insulin trials revealed no safety concerns, with no serious adverse events or symptomatic hypoglycemia in a total ...

7. researchgate.net researchgate.net/publication/244481328_Intranasal_Insulin_to_Treat_and_Protect_Against_Posttraumatic_Stress_Disorder

(PDF) Intranasal Insulin to Treat and Protect Against ... Intranasal insulin has been shown to attenuate the HPA axis and reduce cortisol in adult men exposed to stress [190], which is significant as cortisol blocks ...

8. clinconnect.io clinconnect.io/trials/NCT04044534

Intranasal Insulin for Posttraumatic Stress Disorder To evaluate if intranasal insulin is effective in reducing PTSD symptoms.