Hyperbaric Oxygen Therapy for Prodromal Alzheimer´s Disease With Cerebrovascular Disease: A Prospective, Randomized, Double Blind Study
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Assaf-Harofeh Medical Center
- Enrollment
- 100
- Locations
- 2
- Primary Endpoint
- Change from baseline of neurocognitive functions evaluation by Mindstreams cognitive battery test (Neurotrax)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
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.
Eligibility Criteria
- Ages
- 60 Years to 85 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Diagnosis of Mild cognitive impairment (MCI) due to AD or mixed AD and vascular dementia pathology
- •MMSE score of 20 and above
- •Stable psychological and pharmacological treatment for more than three months prior to inclusion.
- •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
Exclusion Criteria
- •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
- •An inability to perform computerized cognitive tests (Neurotrax)
- •MMSE score below 20
- •No evidence of amyloid in the brain PET
- •No evidence of vascular related lesions in the brain MRI
- •Active smoking
- •Participation in another study
Outcomes
Primary Outcomes
Change from baseline of neurocognitive functions evaluation by Mindstreams cognitive battery test (Neurotrax)
Time Frame: 9 months
Memory, attention and information process will be evaluated using the NeuroTrax computerized cognitive evaluation battery.
Secondary Outcomes
- Brain amyloid PET using Flumetamol (Vizamyl) tracer(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)
- Whole-brain quantitative perfusion imaging(At baseline, 3 months, 9 months)
- Brain microstructure MRI evaluation(At baseline, 3 months, 9 months)