Hyperbaric Oxygen Therapy for Prodromal Alzheimer´s Disease With Cerebrovascular Disease

NCT ID: NCT05349318

Last Updated: 2024-02-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-31
• Study Completion Date: 2025-03-31

Brief Summary

Alzheimer´s disease is a devastating illness that effects the patients as well as their family members. Its prevalence increases exponentially and the burden on the healthcare system is enormous. AD neuropathology begins 15-20 years before the occurrence of cognitive symptoms, which ranges from preclinical stage to mild cognitive impairment (MCI) to dementia. Prodromal AD is an early stage of the disease which is characterized by positive biomarkers and MCI. To this day, there is no medication that can cure or halt the progression of the disease and most studies focus on finding reversible risk factors and changing their influence. Several aetiologies have been proposed, like the deposition of amyloid and tau proteins, neuroinflammation and cerebral ischemia due to cerebrovascular factors. The Amyloid deposition, which serves as the biological marker of AD, was originally thought to be the main cause of the disease, however, recent data suggests that it is not the cause and that it might actually has a protective role. On the other hand, it is known today that vascular changes with related tissue ischemia and neuroinflammation have a crucial role in the development of AD in many patients. These pathologies, ischemia & neuroinflammation, can be improved by the use of hyperbaric oxygen therapy (HBOT). The goal of this study is to explore the potential beneficial effect of HBOT on prodromal AD.

Detailed Description

Alzheimer disease is characterised by cognitive, mental and functional disability that is expected to progress until the patient is fully dependent on others for activities of daily living. The pathology begins many years until the cognitive symptoms appear. Prodromal Alzheimer's disease is a state where a person has mild cognitive impairment and Amyloid deposition, which is seen on brain Amyloid PET or in lumbar puncture.

To date, there has been neither a cure nor a therapy that can significantly halt or relieve symptoms for most patients.

This study offers a new biological therapeutic approach aimed to induce neuroplasticity and improve neurological and cognitive functions. Pre -clinical as well as clinical data indicate that HBOT can be beneficial for those patients who suffer from MCI due to Alzheimer's disease and also to patients with cerebral vascular disease.

HBOT is a well-known treatment used in clinical practice for other indications and is considered to be safe with relative rare mild and reversible side effect .The study is designed as a prospective, randomized, sham controlled double blinded study.

Subjects will be enrolled up to a total of 100 subjects, age 60-85, diagnosed with MCI and positive Amyloid PET and vascular changes on brain MRI.

Eligible patients will be randomized to the two study groups at a ratio of 6:6 (in clusters of 6 patients). The HBOT/sham treatment includes 60 daily sessions of 90 minutes each, five days per week. After the treatment period, there will be a maintenance period of HBOT/sham sessions twice a week for 6 months. All assessments with be done on baseline, after the treatment period and after the maintenance period.

The primary endpoint includes improvement in cognitive scores in neurocognitive evaluations (Neurotrax). Secondary and tertiary endpoints include changes in cognitive, physiological, physical, imaging, lab tests and self report questionaires.

Conditions

Prodromal Alzheimer's Disease; Cerebral Vascular Disorder; Mild Cognitive Impairment; Vascular Cognitive Impairment

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Hyperbaric Oxygen Therapy active arm

The protocol comprises of 60 consecutive hyperbaric oxygen treatment (HBOT) sessions, 5 sessions per week within a three months' period. Then there will be a maintenance period for 6 months in which the participants will receive HBOT twice a week.

Group Type: ACTIVE_COMPARATOR

Hyperbaric oxygen therapy

Intervention Type: DEVICE

Each session will include exposure of 90 minutes to 100% at 2 ATA, with 5 minutes air breaks every 20 minutes

Sham active arm

The protocol comprises of 60 consecutive Sham sessions, 5 sessions per week within a three months' period. Then there will be a maintenance period for 6 months in which the participants will receive Shan sessions twice a week.

Group Type: SHAM_COMPARATOR

Sham

Intervention Type: DEVICE

Each session will include exposure of 90 minutes to 21% at 1.2 ATA during the first five minutes of the session with the noise of circulating air, and then decrease slowly during the next five minutes to 1.03 ATA

Interventions

Hyperbaric oxygen therapy

Each session will include exposure of 90 minutes to 100% at 2 ATA, with 5 minutes air breaks every 20 minutes

Intervention Type: DEVICE

Sham

Each session will include exposure of 90 minutes to 21% at 1.2 ATA during the first five minutes of the session with the noise of circulating air, and then decrease slowly during the next five minutes to 1.03 ATA

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. Diagnosis of Mild cognitive impairment (MCI) due to AD or mixed AD and vascular dementia pathology

2. MMSE score of 20 and above

3. Stable psychological and pharmacological treatment for more than three months prior to inclusion.

4. Caregiver that is seeing the patient at least twice per week and is willing to participate and accompany the patient and fill questionnaires

5. Subject willing and able to read, understand and sign an informed consent

Exclusion Criteria

1. Inability to attend scheduled clinic visits and/or comply with the study protocol

2. History of traumatic brain injury, brain tumors, brain surgery, chronic subdural haemorrhages, Epilepsy

3. Active malignancy

4. Substance use at baseline, except for prescribed cannabis if vaporized or taken PO as tincture

5. History of other neurodegenerative diseases including Parkinson's disease (PD), Lewy body dementia (LBD), Frontotemporal dementia (FTD), Multiple sclerosis (MS), Amyotrophic lateral sclerosis (ALS), Creutzfeld Jacob disease (CJD), Multisystem atrophy (MSA), Pseudobulbar palsy (PSP), Corticobasal degeneration (CBD), Wernicke Korsakoff syndrome

6. Chronic use of medications that may compromise cognitive function and cannot be stopped: Anticonvulsants, Anticholinergics, antiparkinsonian, corticosteroids, Benzodiazepines

7. Moderate to severe sleep apnea with no use of CPAP

8. Diagnosis of a psychiatric disorder including: major depression, schizophrenia, bipolar disorder

9. Serious suicidal ideation

10. Renal or liver insufficiency, electrolyte imbalances

11. Chronic heart failure with ejection fraction of 35 or less

12. HBOT for any reason prior to study enrolment

13. Chest pathology incompatible with pressure changes (including active asthma or COPD)

14. Ear or Sinus pathology incompatible with pressure changes (above 3 otolaryngologist visits a year)

15. An inability to perform an awake brain MRI or Amyloid PET

16. An inability to perform computerized cognitive tests (Neurotrax)

17. MMSE score below 20

18. No evidence of amyloid in the brain PET

19. No evidence of vascular related lesions in the brain MRI

20. Active smoking

21. Participation in another study

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assaf-Harofeh Medical Center

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Karin Elman Shina, MD

Role: PRINCIPAL_INVESTIGATOR

Senior Neurologist and director of the neuropsychology and physiology unit

Locations

Shamir Medical Center (Assaf Harofeh)

Ẕerifin, , Israel

Site Status: RECRUITING

Countries

Israel

Central Contacts

Karin Elman Shina, MD

Role: CONTACT

karine@shamir.gov.il

0097289778061

Facility Contacts

Karin Elman Shina, MD

Role: primary

karine@shamir.gov.il

Other Identifiers

254-21-ASF

Identifier Type: -

Identifier Source: org_study_id