Prodromal Alzheimer's DiseaseNCT05349318
Hyperbaric Oxygen Therapy for Prodromal Alzheimer´s Disease With Cerebrovascular Disease
A study testing Hyperbaric oxygen therapy in people with Prodromal Alzheimer's Disease and Cerebral Vascular Disorder, run by Assaf-Harofeh Medical Center at 1 site in Israel.
Trial 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. Read more about this study
- Who is it for?
- Ages 60 to 85 years
- Conditions the study is for
- Prodromal Alzheimer's Disease, Cerebral Vascular Disorder, Mild Cognitive Impairment
- What is being tested?
- Hyperbaric oxygen therapy
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteIsrael
- Study dates
- 31 Mar 2022to Mar 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
Israel1 site, 1 recruiting
- Recruiting
Shamir Medical Center (Assaf Harofeh)
Tsrifin, 70300
Karin Elman Shina, MD, karine@shamir.gov.il
About this study
Official title: Hyperbaric Oxygen Therapy for Prodromal Alzheimer´s Disease With Cerebrovascular Disease: A Prospective, Randomized, Double Blind Study
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.
Read the 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
- Being tested
- Hyperbaric oxygen therapy, Sham
- Medical subject headings
- Cerebrovascular Disorders, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hyperbaric oxygen therapyDevice
Each session will include exposure of 90 minutes to 100% at 2 ATA, with 5 minutes air breaks every 20 minutes
ShamDevice
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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Device: Sham |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 9 months
Secondary outcomes (5)
Brain amyloid PET using Flumetamol (Vizamyl) tracer
Brain amyloid assessment using PET scan with Flumetamol (Vizamyl) tracer will be used to assess change in amyloid burden
Measured: At baseline, 3 months, 9 months
Whole-brain quantitative perfusion imaging
Whole-brain quantitative perfusion imaging will be performed using Dynamic susceptibility contrast (DSC)-MRI technique
Measured: At baseline, 3 months, 9 months
Brain microstructure MRI evaluation
Fractional anisotropy (FA) and Mean diffusivity (MD) will be evaluated using diffusion tensor imaging (DTI) MRI protocol
Measured: At baseline, 3 months, 9 months
Brain volume MRI evaluation
Gray matter and hippocampal volumetric measurement using high-resolution MP-RAGE 3D MRI
Measured: At baseline, 3 months, 9 months
Brain functional connectivity imaging
Resting state functional MRI
Measured: At baseline ,3 months, 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2022
- Study start31 Mar 2022
- Primary completionAug 2024 (estimated)
- Study completionMar 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prodromal Alzheimer's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assaf-Harofeh Medical Center
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Karin Elman Shina, MD, Principal investigator, Senior Neurologist and director of the neuropsychology and physiology unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05349318
- Sponsor's protocol ID
- 254-21-ASF
- Status last verified
- Feb 2024
- First submitted
- 21 Mar 2022
- Last updated
- 6 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hyperbaric Oxygen Therapy for Prodromal Alzheimer´s Disease With Cerebrovascular Disease: A Prospective, Randomized, Double Blind Study
- ClinicalTrials.gov ID
- NCT05349318
- Acronym / sponsor ID
- 254-21-ASF
- Conditions
- Prodromal Alzheimer's Disease, Cerebral Vascular Disorder, Mild Cognitive Impairment, Vascular Cognitive Impairment
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Assaf-Harofeh Medical CenterOther government
- Study start
- 31 Mar 2022 (actual)
- Primary completion
- Aug 2024 (estimated)
- Study completion
- Mar 2025 (estimated)
- First posted
- 27 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Hyperbaric Oxygen Therapy active arm | Active comparator | Device: Hyperbaric oxygen therapyThe 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. |
| Sham active arm | Sham comparator | Device: ShamThe 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. |
Who may qualify
- Ages
- 60 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hyperbaric oxygen therapyEach session will include exposure of 90 minutes to 100% at 2 ATA, with 5 minutes air breaks every 20 minutes | Device | Hyperbaric Oxygen Therapy active arm |
| ShamEach 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 | Device | Sham active arm |
Primary outcome
Change from baseline of neurocognitive functions evaluation by Mindstreams cognitive battery test (Neurotrax)
Time frame: At baseline, 3 months
Memory, attention and information process will be evaluated using the NeuroTrax computerized cognitive evaluation battery.
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.
5 secondary outcomes
Brain amyloid PET using Flumetamol (Vizamyl) tracer
Time frame: At baseline, 3 months, 9 months
Whole-brain quantitative perfusion imaging
Time frame: At baseline, 3 months, 9 months
Brain microstructure MRI evaluation
Time frame: At baseline, 3 months, 9 months
Brain volume MRI evaluation
Time frame: At baseline, 3 months, 9 months
Brain functional connectivity imaging
Time frame: At baseline ,3 months, 9 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Karin Elman Shina, MD principal investigator
Senior Neurologist and director of the neuropsychology and physiology unit
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Hyperbaric oxygen therapy in people with Prodromal Alzheimer's Disease and Cerebral Vascular Disorder, run by Assaf-Harofeh Medical Center at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Karin Elman Shina, MD (0097289778061, karine@shamir.gov.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline of neurocognitive functions evaluation by Mindstreams cognitive battery test (Neurotrax) (time frame: At baseline, 3 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2024.