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

NCT05349318 | Recruiting

• 1 other identifier: 254-21-ASF
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Change from baseline of neurocognitive functions evaluation by Mindstreams cognitive battery test (Neurotrax)

  Memory, attention and information process will be evaluated using the NeuroTrax computerized cognitive evaluation battery.

  At baseline, 3 months

• Change from baseline of neurocognitive functions evaluation by Mindstreams cognitive battery test (Neurotrax)

  Memory, attention and information process will be evaluated using the NeuroTrax computerized cognitive evaluation battery.

  9 months

Secondary Outcomes (5)

• Brain amyloid PET using Flumetamol (Vizamyl) tracer

  At baseline, 3 months, 9 months

• Whole-brain quantitative perfusion imaging

  At baseline, 3 months, 9 months

• Brain microstructure MRI evaluation

  At baseline, 3 months, 9 months

• Brain volume MRI evaluation

  At baseline, 3 months, 9 months

• Brain functional connectivity imaging

  At baseline ,3 months, 9 months

Other Outcomes (31)

• Quality of life SF-36 questionnaire

  At baseline, 3 months, 9 months

• The Pittsburgh Sleep Quality Index (PSQI) questionnaire

  At baseline, 3 months, 9 months

• The Depression, Anxiety and Stress Scale-21 (DASS-21)

  At baseline, 3 months, 9 months

Study Arms (2)

Hyperbaric Oxygen Therapy active arm

ACTIVE COMPARATOR

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.

Device: Hyperbaric oxygen therapy

Sham active arm

SHAM COMPARATOR

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.

Device: Sham

Interventions

Hyperbaric oxygen therapy DEVICE

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

Hyperbaric Oxygen Therapy active arm

Sham 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

Sham active arm

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of Mild cognitive impairment (MCI) due to AD or mixed AD and vascular dementia pathology
• MMSE score of 20 and above
• Caregiver that is seeing the patient at least twice per week and is willing to participate and accompany the patient and fill questionnaires
• Subject willing and able to read, understand and sign an informed consent

You may not qualify if:

• Inability to attend scheduled clinic visits and/or comply with the study protocol
• History of traumatic brain injury, brain tumors, brain surgery, chronic subdural haemorrhages, Epilepsy
• Active malignancy
• Substance use at baseline, except for prescribed cannabis if vaporized or taken PO as tincture
• 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
• Chronic use of medications that may compromise cognitive function and cannot be stopped: Anticonvulsants, Anticholinergics, antiparkinsonian, corticosteroids, Benzodiazepines
• Moderate to severe sleep apnea with no use of CPAP
• Diagnosis of a psychiatric disorder including: major depression, schizophrenia, bipolar disorder
• Serious suicidal ideation
• Renal or liver insufficiency, electrolyte imbalances
• Chronic heart failure with ejection fraction of 35 or less
• HBOT for any reason prior to study enrolment
• Chest pathology incompatible with pressure changes (including active asthma or COPD)
• Ear or Sinus pathology incompatible with pressure changes (above 3 otolaryngologist visits a year)
• An inability to perform an awake brain MRI or Amyloid PET

Sponsors & Collaborators

• Assaf-Harofeh Medical Center: lead

Study Sites (1)

Shamir Medical Center (Assaf Harofeh)

Ẕerifin, 70300, Israel

RECRUITING

MeSH Terms

Conditions

Cerebrovascular Disorders; Cognitive Dysfunction

Interventions

Hyperbaric Oxygenation

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Oxygen Inhalation Therapy; Respiratory Therapy; Therapeutics

Study Officials

• Karin Elman Shina, MD

  Senior Neurologist and director of the neuropsychology and physiology unit

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Karin Elman Shina, MD

CONTACT

0097289778061; karine@shamir.gov.il

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Eligible candidates will be randomized with equal probability to the HBOT and sham interventions. Randomization will be performed using a computer software based on patients' code. Since the HBOT chamber can hold six subjects, the randomization will be done in clusters of six patients. After randomization, when a cluster of six subjects from one of the arms will be filled, the intervention for that cluster will begin. Three study technicians will be the only unblinded staff who have the key for the group assignment of each subject. They will exclusively activate the HBOT/sham protocol during session times. All subjects and other clinic staff will remain blinded to the group assignments.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Upon consent and evaluation, eligible participants will be randomized with equal probability into one of two arms: HBOT or SHAM. The evaluation procedure will be performed at baseline, after the treatment and after a maintenance period.

Study Record Dates

• First Submitted: March 21, 2022
• First Posted: April 27, 2022
• Study Start: March 31, 2022
• Primary Completion: August 1, 2024
• Study Completion: March 1, 2025
• Last Updated: February 6, 2024

Record last verified: 2024-02

Locations

IL (1)