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

Trial Summary

What is the purpose of this trial?

Single-blind, randomized controlled trial of normobaric oxygen therapy among individuals with first-episode psychosis: Effects on symptomatology and cognition.

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 data supports the effectiveness of the treatment 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 oxygen therapies might help improve symptoms in psychosis. Additionally, home treatment approaches, which can include oxygen therapy, have been beneficial for managing acute psychotic episodes. ^{1 2 3 4 5}

Is normobaric oxygen therapy safe for humans?

Normobaric oxygen therapy (NBO) has been studied for conditions like ischemic stroke and is generally considered safe. However, it is important to note that while hyperbaric oxygen therapy (a different treatment) can have side effects like ear discomfort and claustrophobia, these are not typically associated with normobaric oxygen therapy. ^{6 7 8 9 10}

How is normobaric oxygen therapy different from other treatments for first-episode psychosis?

Normobaric oxygen therapy is unique because it involves breathing in 100% oxygen at normal atmospheric pressure, which is different from typical medications or therapies for psychosis. This treatment is being explored for its potential neuroprotective effects, as seen in studies related to stroke, but its effectiveness for psychosis is still under investigation. ^{6 7 9 11 12}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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]

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]

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 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 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]

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]

References

1. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Clinical effectiveness of hyperbaric oxygenation in the combined treatment of patients with schizophrenia]. [2007]

2. England pubmed.ncbi.nlm.nih.gov

Cognitive--behavioural therapy and family intervention for relapse prevention and symptom reduction in psychosis: randomised controlled trial. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

A randomized controlled trial of relapse prevention therapy for first-episode psychosis patients: outcome at 30-month follow-up. [2021]

4. England pubmed.ncbi.nlm.nih.gov

The outcomes of home treatment for schizophrenia. [2020]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Cognitive therapy for schizophrenia: a preliminary randomized controlled trial. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Magnetic resonance spectroscopy study of oxygen therapy in ischemic stroke. [2016]

7. United States pubmed.ncbi.nlm.nih.gov

Normobaric Hyperoxia Combined With Endovascular Treatment for Patients With Acute Ischemic Stroke: A Randomized Controlled Clinical Trial. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Side effects of hyperbaric oxygen therapy. [2014]

9. United States 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. [2023]

10. Austria pubmed.ncbi.nlm.nih.gov

Effect of hyperbaric oxygen on patients with traumatic brain injury. [2019]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Normobaric Oxygen Therapy in Acute Stroke: A Systematic Review and Meta-Analysis. [2022]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Oxygen therapy in permanent brain ischemia: potential and limitations. [2015]