Ignite Creation Date:
2025-12-25 @ 4:52 AM
Ignite Modification Date:
2025-12-26 @ 3:53 AM
Study NCT ID:
NCT05349318
Status:
RECRUITING
Last Update Posted:
2024-02-06
First Post:
2022-03-21
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Hyperbaric Oxygen Therapy for Prodromal Alzheimer´s Disease With Cerebrovascular Disease
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D002561', 'term': 'Cerebrovascular Disorders'}, {'id': 'D060825', 'term': 'Cognitive Dysfunction'}], 'ancestors': [{'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D003072', 'term': 'Cognition Disorders'}, {'id': 'D019965', 'term': 'Neurocognitive Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D006931', 'term': 'Hyperbaric Oxygenation'}], 'ancestors': [{'id': 'D010102', 'term': 'Oxygen Inhalation Therapy'}, {'id': 'D012138', 'term': 'Respiratory Therapy'}, {'id': 'D013812', 'term': 'Therapeutics'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR'], 'maskingDescription': "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.\n\nSince 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.\n\nThree 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."}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': '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.'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 100}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2022-03-31', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-02', 'completionDateStruct': {'date': '2025-03', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2024-02-05', 'studyFirstSubmitDate': '2022-03-21', 'studyFirstSubmitQcDate': '2022-04-24', 'lastUpdatePostDateStruct': {'date': '2024-02-06', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2022-04-27', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2024-08', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Quality of life SF-36 questionnaire', 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'Self reported SF-36 quality of life questionnaire'}, {'measure': 'The Pittsburgh Sleep Quality Index (PSQI) questionnaire', 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'Self reported quality of sleep questionnaire'}, {'measure': 'The Depression, Anxiety and Stress Scale-21 (DASS-21)', 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'Self reported questionnaire of depression, anxiety and stress'}, {'measure': 'Advanced Activities of Daily Function (a-ADL)', 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'Questionnaire of activities of daily living for the patient and the informant'}, {'measure': 'Clinical Dementia Rating (CDR) scale - sum of boxes', 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'Cognitive assessment of 6 cognitive and functional domains, based on an interview of the patient and a reliable informant'}, {'measure': 'Montreal Cognitive Assessment (MOCA)', 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'Neurocognitive assessment'}, {'measure': 'Mini Mental State Exam (MMSE)', 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'Neurocognitive assessment'}, {'measure': 'Serum inflammatory markers', 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'Serum inflammatory markers include: IL-1, IL-6, tumor necrosis factor-alpha, hsCRP'}, {'measure': "Alzheimer's disease (AD) biomarkers: Abeta 42/40", 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'Plasma will be tested for Abeta 42/40'}, {'measure': "Alzheimer's disease (AD) biomarkers: P-tau181", 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'Plasma will be tested for P-tau181'}, {'measure': "Alzheimer's disease (AD) biomarkers: P-tau231", 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'Plasma will be tested for P-tau 231'}, {'measure': "Alzheimer's disease (AD) biomarkers: neurofilament light (NfL)", 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'Plasma will be tested for neurofilament light (NfL)'}, {'measure': "Alzheimer's disease (AD) biomarkers: plasma glial fibrillary acidic protein (GFAP)", 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'Plasma will be tested for plasma glial fibrillary acidic protein (GFAP)'}, {'measure': 'Vascular biomarker- Vascular endothelial growth factor (VEGF)', 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'Serum will be tested for VEGF'}, {'measure': 'Passive behavioral monitoring using BHQ smartphone application', 'timeFrame': 'Through study completion, up to one year', 'description': "An application will be installed on the participants' smartphones for continuous passive monitoring of human behavior"}, {'measure': 'Cardiopulmonary exercise test (CPET)', 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'CPET determines the anaerobic threshold that is expected to change through the intervention'}, {'measure': 'Neuro-physical evaluation - Static balance', 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'Static balance will be assessed by the Balance Error Scoring System (BESS)'}, {'measure': 'Neuro-physical evaluation- Timed Up and Go test', 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'Dynamic balance and risk of falling will be assessed by the Timed Up and Go test (TUG)'}, {'measure': 'Neuro-physical evaluation - 10 meter walk', 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'Dynamic balance and risk of falling will be assessed by 10-meter walk (10MW).'}, {'measure': 'Neuro-physical evaluation - Sit to Stand test', 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'Muscle function will be assessed by the sit to stand (STS) test for the leg strength and endurance'}, {'measure': 'Neuro-physical evaluation - Hand held dynamometery', 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'Muscle function will be assessed by the hand-held dynamometry (HHD) for the isometric grip strength.'}, {'measure': 'Neuro-physical evaluation - 6 minute walk', 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'The sub-maximal aerobic capacity and endurance will be assessed by the 6-minute walk test (6MWT).'}, {'measure': 'Event-related synchronization (ERS) change - EEG', 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'The EEG will include a three-level visual N-back task, and go-no-go task'}, {'measure': 'Event-related desynchronization (ERD) change - EEG', 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'The EEG will include a three-level visual N-back task, and go-no-go task'}, {'measure': 'Grand average P300 ERP change - EEG', 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'The EEG will include a three-level visual N-back task, and go-no-go task'}, {'measure': 'Alpha band power change - EEG', 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'The EEG will include a three-level visual N-back task, and go-no-go task'}, {'measure': 'Beta band power change - EEG', 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'The EEG will include a three-level visual N-back task, and go-no-go task'}, {'measure': 'Gamma band power change - EEG', 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'The EEG will include a three-level visual N-back task, and go-no-go task'}, {'measure': 'Delta band power change - EEG', 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'The EEG will include a three-level visual N-back task, and go-no-go task'}, {'measure': 'Theta to alpha bands power ratio change - EEG', 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'The EEG will include a three-level visual N-back task, and go-no-go task'}, {'measure': 'N-back match/no match percentage change - EEG', 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'The EEG will include a three-level visual N-back task, and go-no-go task'}], 'primaryOutcomes': [{'measure': 'Change from baseline of neurocognitive functions evaluation by Mindstreams cognitive battery test (Neurotrax)', 'timeFrame': 'At baseline, 3 months', 'description': 'Memory, attention and information process will be evaluated using the NeuroTrax computerized cognitive evaluation battery.'}, {'measure': 'Change from baseline of neurocognitive functions evaluation by Mindstreams cognitive battery test (Neurotrax)', 'timeFrame': '9 months', 'description': 'Memory, attention and information process will be evaluated using the NeuroTrax computerized cognitive evaluation battery.'}], 'secondaryOutcomes': [{'measure': 'Brain amyloid PET using Flumetamol (Vizamyl) tracer', 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'Brain amyloid assessment using PET scan with Flumetamol (Vizamyl) tracer will be used to assess change in amyloid burden'}, {'measure': 'Whole-brain quantitative perfusion imaging', 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'Whole-brain quantitative perfusion imaging will be performed using Dynamic susceptibility contrast (DSC)-MRI technique'}, {'measure': 'Brain microstructure MRI evaluation', 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'Fractional anisotropy (FA) and Mean diffusivity (MD) will be evaluated using diffusion tensor imaging (DTI) MRI protocol'}, {'measure': 'Brain volume MRI evaluation', 'timeFrame': 'At baseline, 3 months, 9 months', 'description': 'Gray matter and hippocampal volumetric measurement using high-resolution MP-RAGE 3D MRI'}, {'measure': 'Brain functional connectivity imaging', 'timeFrame': 'At baseline ,3 months, 9 months', 'description': 'Resting state functional MRI'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ["Prodromal Alzheimer's Disease", 'Cerebral Vascular Disorder', 'Mild Cognitive Impairment', 'Vascular Cognitive Impairment']}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': "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.\n\nTo date, there has been neither a cure nor a therapy that can significantly halt or relieve symptoms for most patients.\n\nThis 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.\n\nHBOT 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.\n\nSubjects 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.\n\nEligible 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.\n\nThe 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."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '85 Years', 'minimumAge': '60 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n1. Diagnosis of Mild cognitive impairment (MCI) due to AD or mixed AD and vascular dementia pathology\n2. MMSE score of 20 and above\n3. Stable psychological and pharmacological treatment for more than three months prior to inclusion.\n4. Caregiver that is seeing the patient at least twice per week and is willing to participate and accompany the patient and fill questionnaires\n5. Subject willing and able to read, understand and sign an informed consent\n\nExclusion Criteria:\n\n1. Inability to attend scheduled clinic visits and/or comply with the study protocol\n2. History of traumatic brain injury, brain tumors, brain surgery, chronic subdural haemorrhages, Epilepsy\n3. Active malignancy\n4. Substance use at baseline, except for prescribed cannabis if vaporized or taken PO as tincture\n5. 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\n6. Chronic use of medications that may compromise cognitive function and cannot be stopped: Anticonvulsants, Anticholinergics, antiparkinsonian, corticosteroids, Benzodiazepines\n7. Moderate to severe sleep apnea with no use of CPAP\n8. Diagnosis of a psychiatric disorder including: major depression, schizophrenia, bipolar disorder\n9. Serious suicidal ideation\n10. Renal or liver insufficiency, electrolyte imbalances\n11. Chronic heart failure with ejection fraction of 35 or less\n12. HBOT for any reason prior to study enrolment\n13. Chest pathology incompatible with pressure changes (including active asthma or COPD)\n14. Ear or Sinus pathology incompatible with pressure changes (above 3 otolaryngologist visits a year)\n15. An inability to perform an awake brain MRI or Amyloid PET\n16. An inability to perform computerized cognitive tests (Neurotrax)\n17. MMSE score below 20\n18. No evidence of amyloid in the brain PET\n19. No evidence of vascular related lesions in the brain MRI\n20. Active smoking\n21. Participation in another study"}, 'identificationModule': {'nctId': 'NCT05349318', 'briefTitle': 'Hyperbaric Oxygen Therapy for Prodromal Alzheimer´s Disease With Cerebrovascular Disease', 'organization': {'class': 'OTHER_GOV', 'fullName': 'Assaf-Harofeh Medical Center'}, 'officialTitle': 'Hyperbaric Oxygen Therapy for Prodromal Alzheimer´s Disease With Cerebrovascular Disease: A Prospective, Randomized, Double Blind Study', 'orgStudyIdInfo': {'id': '254-21-ASF'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Hyperbaric Oxygen Therapy active arm', 'description': "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.", 'interventionNames': ['Device: Hyperbaric oxygen therapy']}, {'type': 'SHAM_COMPARATOR', 'label': 'Sham active arm', 'description': "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.", 'interventionNames': ['Device: Sham']}], 'interventions': [{'name': 'Hyperbaric oxygen therapy', 'type': 'DEVICE', 'description': 'Each session will include exposure of 90 minutes to 100% at 2 ATA, with 5 minutes air breaks every 20 minutes', 'armGroupLabels': ['Hyperbaric Oxygen Therapy active arm']}, {'name': 'Sham', 'type': 'DEVICE', 'description': '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', 'armGroupLabels': ['Sham active arm']}]}, 'contactsLocationsModule': {'locations': [{'zip': '70300', 'city': 'Ẕerifin', 'status': 'RECRUITING', 'country': 'Israel', 'contacts': [{'name': 'Karin Elman Shina, MD', 'role': 'CONTACT', 'email': 'karine@shamir.gov.il'}], 'facility': 'Shamir Medical Center (Assaf Harofeh)', 'geoPoint': {'lat': 31.95731, 'lon': 34.84852}}], 'centralContacts': [{'name': 'Karin Elman Shina, MD', 'role': 'CONTACT', 'email': 'karine@shamir.gov.il', 'phone': '0097289778061'}], 'overallOfficials': [{'name': 'Karin Elman Shina, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Senior Neurologist and director of the neuropsychology and physiology unit'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Assaf-Harofeh Medical Center', 'class': 'OTHER_GOV'}, 'responsibleParty': {'type': 'SPONSOR'}}}}