Normobaric Oxygen Therapy for First-Episode Psychosis

Overseen By Nicholas Breitborde, PhD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Nicholas Breitborde

Disqualifiers: Intellectual disability, Smoker, Suicidal ideation, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 4 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether inhaling higher levels of oxygen at night can help individuals experiencing their first episode of psychosis, which includes symptoms like hallucinations or delusions. The trial will compare two groups: one using normal air and the other using air with a higher oxygen level (Normobaric Oxygen Therapy). The goal is to determine if oxygen therapy can improve symptoms and cognitive abilities. The trial seeks participants diagnosed with a schizophrenia-related disorder or a mood disorder with psychotic features, who have had symptoms for less than five years and are non-smokers. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new treatment options.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that normobaric oxygen therapy is safe for individuals with first-episode psychosis?

Research has shown that normobaric oxygen therapy with 40% oxygen is safe. Studies on animals and humans have found no lung damage at this oxygen level, indicating that the treatment does not harm the lungs, even with repeated use.

However, oxygen therapy may require special care for individuals with conditions such as severe anxiety or psychosis. Overall, evidence suggests it is generally well-tolerated.

For prospective trial participants, this information demonstrates strong safety data for normobaric oxygen therapy. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for first-episode psychosis, which often involve antipsychotic medications targeting neurotransmitter imbalances, normobaric oxygen therapy offers a novel approach by using enhanced oxygen levels. This therapy stands out because it delivers oxygen at a higher concentration (40% FiO2) than normal room air, potentially reducing oxidative stress and inflammation in the brain, which are thought to contribute to psychosis. Researchers are excited because this method could provide a non-invasive, drug-free option that might work faster and with fewer side effects than traditional medication.

What evidence suggests that normobaric oxygen therapy might be an effective treatment for first-episode psychosis?

This trial will compare Normobaric Oxygen Therapy with a placebo condition for individuals experiencing their first episode of psychosis. Research has shown that breathing normal levels of oxygen might benefit those experiencing psychosis for the first time. One study on a similar treatment, where patients inhaled higher levels of oxygen, showed positive effects when combined with medication for people with schizophrenia. This suggests that increasing oxygen in the body could help improve mental health symptoms. Another study found that breathing normal levels of oxygen helped individuals with mild-to-moderate depression, indicating potential benefits for mood disorders. These findings suggest that this oxygen therapy could reduce symptoms and improve cognitive function in people experiencing their first episode of psychosis. ^{3 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for young adults aged 15-35 who have recently experienced their first episode of psychosis, specifically schizophrenia or mood disorders with psychotic features. Participants must be non-smokers without suicidal thoughts in the past month and have an IQ above 70.

Inclusion Criteria

No evidence of a pre-existing intellectual disability defined as a premorbid IQ >70 as estimated using the Reading subtest of the Wide Range Achievement Test-4

I have been diagnosed with schizophrenia or a mood disorder with psychosis.

You do not have a pre-existing intellectual disability, which means your IQ was measured to be above 70 before you got sick.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 4 weeks of nightly normobaric oxygen therapy or placebo condition

4 weeks

1 visit (in-person) at enrollment

Open-label extension

All participants receive an additional 4 weeks of unblinded nightly normobaric oxygen therapy

4 weeks

1 visit (in-person) at 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person) at 8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Normobaric Oxygen
• Placebo

Trial Overview The study is testing if breathing normobaric oxygen can help with symptoms and thinking abilities in people with first-time psychosis. It's a single-blind trial where some get real oxygen therapy and others get a placebo, decided randomly.

How Is the Trial Designed?

Group I: Normobaric Oxygen Therapy (40% FiO2) Experimental Treatment 1 Intervention

4 weeks of nightly normobaric oxygen therapy (40% FiO2)

Group II: Placebo Condition Placebo Group 1 Intervention

4 weeks of a placebo condition utilizing room air oxygen levels (21% FiO2)

Normobaric Oxygen is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Normobaric Oxygen Therapy for:

• Chronic obstructive pulmonary disease (COPD)
• Cystic fibrosis
• Heart failure
• Asthma
• Pulmonary hypertension
• General breathing issues

Approved in United States as Normobaric Oxygen Therapy for:

• Acute stroke
• Neurological trauma
• Carbon monoxide poisoning
• Respiratory conditions

Approved in Canada as Normobaric Oxygen Therapy for:

• Respiratory conditions
• Neurological conditions

Who Is Running the Clinical Trial?

Nicholas Breitborde

Lead Sponsor

Trials

2

Recruited

20+

Published Research Related to This Trial

Normobaric oxygen therapy (NBO) appears to be neuroprotective in acute ischemic stroke, as shown by imaging studies that indicate improved metabolic markers in patients treated with NBO compared to those receiving room air.

Patients receiving NBO showed a decrease in lactate levels during treatment and maintained N-acetyl-aspartate levels, suggesting that NBO enhances aerobic metabolism and helps preserve neuronal integrity in the affected brain areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance spectroscopy study of oxygen therapy in ischemic stroke. Singhal, AB., Ratai, E., Benner, T., et al.[2016]

In a pilot study involving 86 patients with acute ischemic stroke, the combination of normobaric hyperoxia (NBO) and endovascular treatment (EVT) significantly reduced infarct volume compared to EVT alone, with median volumes of 20.1 mL versus 37.7 mL (p < 0.01).

Patients receiving NBO + EVT also showed improved clinical outcomes at 90 days, with a median modified Rankin Scale (mRS) score of 2 compared to 3 in the EVT group (p = 0.038), suggesting better functional recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Normobaric Hyperoxia Combined With Endovascular Treatment for Patients With Acute Ischemic Stroke: A Randomized Controlled Clinical Trial. Li, W., Qi, Z., Ma, Q., et al.[2023]

A systematic review of 15 studies involving 9,255 participants found that normobaric oxygen (NBO) therapy did not significantly improve early neurological recovery or functional outcomes in patients with acute stroke.

Most studies used low-flow oxygen and started treatment in the sub-acute phase, suggesting that the timing and delivery method of oxygen therapy may not have been optimal for neuroprotection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Normobaric Oxygen Therapy in Acute Stroke: A Systematic Review and Meta-Analysis. Mahmood, A., Neilson, S., Biswas, V., et al.[2022]

Both normobaric hyperoxia (NBH) and hyperbaric oxygen therapy (HBOT) significantly improve cognitive outcomes in patients with mild traumatic brain injury (TBI), as evidenced by better scores on cognitive assessments like MoCA and MMSE.

HBOT is more effective than NBH in enhancing cognitive function and reducing biomarkers of brain injury, indicating that higher pressure oxygen therapy may provide superior benefits for patients recovering from mild TBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HBOT has a better cognitive outcome than NBH for patients with mild traumatic brain injury: A randomized controlled clinical trial. Liu, Z., Wang, X., Wu, Z., et al.[2023]

In a study involving 301 patients with non-affective psychosis, neither cognitive-behavioral therapy (CBT) nor family intervention significantly reduced relapse rates or improved remission outcomes over 12 or 24 months.

While CBT did not prevent relapses, it showed some benefits in reducing depression and improving social functioning and delusional distress in patients with carers, suggesting that CBT may be more useful for managing specific symptoms rather than as a general relapse prevention strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive--behavioural therapy and family intervention for relapse prevention and symptom reduction in psychosis: randomised controlled trial. Garety, PA., Fowler, DG., Freeman, D., et al.[2021]

Intensive home treatment (IHTT) for acute schizophrenia was beneficial, with three-quarters of the 245 individuals showing improvement in their condition as measured by the Clinical Global Impression (CGI) scale.

IHTT allowed for safe management of severe acute psychotic episodes at home, highlighting its effectiveness in improving clinical outcomes while addressing the common issue of medication polypharmacy and substance misuse in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The outcomes of home treatment for schizophrenia. Huang, HCH., Taylor, M., Carmichael, A.[2020]

In a study of 44 subacute traumatic brain injury (TBI) patients, those who received hyperbaric oxygen therapy (HBOT) showed a significant improvement in their Glasgow Coma Scale (GCS) scores, indicating better neurological function compared to the control group.

Patients treated with HBOT also demonstrated notable improvements in their Glasgow Outcome Scale (GOS) scores after 6 months, suggesting that HBOT can positively impact recovery in TBI patients with minimal adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of hyperbaric oxygen on patients with traumatic brain injury. Lin, JW., Tsai, JT., Lee, LM., et al.[2019]

A 7-month psychosocial treatment for preventing relapse in first-episode psychosis showed a significantly lower relapse rate and delayed time to relapse at the 12-month follow-up compared to standard specialist care, with 41 patients in the treatment group and 40 in the control group.

Despite initial positive effects, the experimental group experienced a deterioration in psychosocial functioning over time, raising questions about the long-term efficacy of the treatment and the role of medication adherence in these outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial of relapse prevention therapy for first-episode psychosis patients: outcome at 30-month follow-up. Gleeson, JF., Cotton, SM., Alvarez-Jimenez, M., et al.[2021]

In a study of 42 patients with schizophrenia, those receiving cognitive-behavioral therapy (CBT) alongside enriched standard treatment showed improvements in overall symptom severity, particularly in negative symptoms, after 6 months of therapy.

While there were no significant differences between the CBT group and the standard treatment group immediately after treatment, the follow-up results indicated that CBT may be particularly effective in reducing negative symptoms over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive therapy for schizophrenia: a preliminary randomized controlled trial. Rector, NA., Seeman, MV., Segal, ZV.[2019]

In a study comparing normobaric (NBO) and hyperbaric (HBO) oxygen therapies in mice with permanent cerebral ischemia, HBO was found to be more effective than NBO in reducing brain infarct size when treatment was initiated shortly after the ischemic event.

The combination of NBO and HBO therapy resulted in smaller infarcts compared to NBO alone, suggesting that using both therapies together can enhance protective effects against brain damage in permanent ischemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxygen therapy in permanent brain ischemia: potential and limitations. Veltkamp, R., Sun, L., Herrmann, O., et al.[2015]

Hyperbaric oxygenation (HBO) treatment combined with psychopharmacotherapy showed promising results in 50 patients with drug-resistant schizophrenia, particularly those experiencing asthenic and apathetic depressions.

The most significant therapeutic effects were observed after 10-12 sessions of HBO, suggesting that this treatment could be beneficial for specific forms of schizophrenia with associated psychological disturbances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical effectiveness of hyperbaric oxygenation in the combined treatment of patients with schizophrenia]. Isakov, IuV., Churkin, EA., Epifanova, NM., et al.[2007]

The most common side effects of hyperbaric oxygen (HBO2) therapy are middle ear barotrauma, affecting up to 2% of patients, which can be managed through techniques like autoinflation or tympanostomy tubes.

While rare, more severe side effects from HBO2 therapy can include oxygen toxicity leading to issues like progressive myopia and pulmonary dyspnea, with serious complications like seizures occurring at higher oxygen pressures, particularly in patients with acidosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side effects of hyperbaric oxygen therapy. Camporesi, EM.[2014]

Citations

1. withpower.com withpower.com/trial/phase-schizophrenia-11-2019-bc55b

Normobaric Oxygen Therapy for First-Episode Psychosis Research on hyperbaric oxygenation (a similar oxygen therapy) in schizophrenia patients showed positive effects when combined with medication, suggesting that ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6181555/

Treatment with normobaric or hyperbaric oxygen and its ... The meta-analysis indicated that compared with CO poisoning patients treated with NBO, HBO treated patients have a lower incidence of neuropsychological ...

3. nature.com nature.com/articles/s41598-021-98245-9

Normobaric oxygen treatment for mild-to-moderate ... This study examined the efficacy of normobaric oxygen treatment in subjects with depression. In a randomized, double-blind trial, 55 participants aged 18–65 ...

4. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/237731

Normobaric Oxygen Therapy for Individuals With First-Episode ... Single-blind, randomized controlled trial of normobaric oxygen therapy among individuals with first-episode psychosis: Effects on symptomatology and cognition.

5. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/237731

Normobaric Oxygen Therapy for Individuals With First- ... Single-blind, randomized controlled trial of normobaric oxygen therapy among individuals with first-episode psychosis: Effects on symptomatology ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8460750/

Normobaric oxygen treatment for mild-to-moderate ... Normobaric oxygen treatment at a concentration of 40% was found safe in animal and human studies without evidence of pulmonary oxygen toxicity ...

7. assets.hpra.ie assets.hpra.ie/products/Human/29566/Licence_PA1848-005-003_30042024151138.pdf

Summary of Product Characteristics The benefit/risk ratio of HBOT should be thoroughly evaluated in patients with claustrophobia, severe anxiety and psychosis. Diabetic ...