Hyperbaric Oxygen Therapy for Cognition in Diabetic Elderly at High Dementia Risk

Sponsor
Icahn School of Medicine at Mount Sinai (Other)
Overall Status
Recruiting
CT.gov ID
NCT03036254
Collaborator
Sheba Medical Center (Other), Assaf-Harofeh Medical Center (Other), University of Wisconsin, Madison (Other)
154
4
2
74.8
38.5
0.5

Study Details

Study Description

Brief Summary

An urgent need exists to identify effective interventions to arrest or reverse dementia and cognitive loss at its earliest stages. The proposed pilot randomized clinical trial will investigate the short and long-term effects of hyperbaric oxygen therapy on cognitive functioning, cerebral blood flow, and glucose uptake in diabetic elderly with mild cognitive impairment. and provide the basis for a large-scale multi-center study of hyperbaric oxygen therapy effects on cognition in diabetes. The potential to preserve, or even enhance, cognition in elderly at high risk of cognitive decline and dementia has major implications for the affected individuals and their support systems that bear the social and financial burdens of long-term caregiving.

Condition or Disease Intervention/Treatment Phase
  • Device: HBOT intervention
  • Device: Sham intervention
N/A

Detailed Description

This resubmission responds to "PAR-16-365-Pilot Clinical Trials for the Spectrum of Alzheimer's Disease and Age-related Cognitive Decline (R01)". It will examine the efficacy of hyperbaric oxygen therapy (HBOT) in improving cognitive functioning in cognitively impaired elderly with diabetes (T2D), who have high risk for dementia. It is a collaboration of the Icahn School of Medicine at Mount Sinai, NY, the University of Wisconsin, the Sagol Center for Hyperbaric Medicine and Research at Asaf Harofeh Medical Center, Israel-one of the world's largest and busiest hyperbaric units-and the Sheba Medical Center, Israel.

HBOT is a treatment in which oxygen-enriched air (up to 100%) is administered to patients at a pressure above the ambient atmosphere. The combined action of hyperoxia and hyperbaric pressure leads to significant improvements in tissue oxygenation, resulting in cerebrovascular benefits with improved ischemic damage and cerebral blood flow. Recently, the researchers of this group published compelling evidence from clinical trials indicating HBOT neurotherapeutic effects in stroke, with better cognitive function and elevated brain activity in SPECT. New preliminary data suggests potential neurotherapeutic effects of HBOT on T2D elderly with mild cognitive impairment (MCI), showing better cognitive performance and brain activity. The researchers propose a randomized controlled clinical trial examining the short (12 weeks) and long-term (12 months) efficacy of HBOT. The researchers will test hypotheses that HBOT compared to a sham condition improves cognitive function and increases cerebral blood flow and glucose utilization in MCI patients with T2D. Such patients are at high dementia risk and enriched in cerebrovascular disease, and thus have high potential for benefitting from HBOT. Aim 1 examines the potential beneficial effects of HBOT on cognition (with a primary composite measure of executive functions and episodic memory, both affected by T2D). Aim 2 examines effects of HBOT on ischemic injury which will be measured by CBF at the level of capillaries in gray matter (by MRI arterial spin labeling), and in macrovessels (by a novel 4D Flow MRI technology developed by the researchers of this group). Aim 3 focuses on effects of HBOT on cerebral glucose utilization using [F18]FDG-PET. Finally, Aim 4 investigates mediation by the biomarkers, i.e. whether their inclusion in a mediation model will attenuate the effect of HBOT on cognition, suggesting them as underlying mechanisms. This study will be performed in Israel, where there is optimal infrastructure and expertise for all the study components at significantly lower costs. HBOT can be widely deployed in the US so if successful, this pilot study will provide the basis for a multi-center large-scale clinical trial for definitive evidence of its benefits to cognition in T2D patients at high dementia risk. Despite advances in the understanding of risk factors and the pathologic basis for dementia, treatments are of very limited effects. As the proportion of elderly increases, the accelerating prevalence of T2D and dementia amplifies this application's public health impact.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
154 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
Hyperbaric Oxygen Therapy for Cognition in Diabetic Elderly at High Dementia Risk
Actual Study Start Date :
Oct 8, 2017
Anticipated Primary Completion Date :
Jan 1, 2024
Anticipated Study Completion Date :
Jan 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: HBOT intervention

The multiplace HBOT unit at Asaf Harofeh. The inside looks like an airplane, with comfortable chairs for 11 subjects and the nurse who stays throughout the session. The HBOT protocol is 90 minutes, 5 times/week, 60 sessions, 100% oxygen at 2 ATA with 5 minute air breaks every 30 minutes.

Device: HBOT intervention
HBOT is a treatment in which oxygen-enriched air (up to 100%) is administered to patients at a pressure. HBOT intervention arm - 3 months of HBOT treatment, 9 months observation all participants receive HBOT treatment for 3 months at year 2
Other Names:
  • Hyperbaric oxygen therapy
  • Sham Comparator: Sham intervention

    Except for pressure, all the conditions of the HBOT intervention are provided in the sham intervention (nurse measures vitals and asks about health before entering the chamber, time in the chamber, number of sessions per week and overall, nurse in the chamber at all times, mask on the face, etc.).

    Device: HBOT intervention
    HBOT is a treatment in which oxygen-enriched air (up to 100%) is administered to patients at a pressure. HBOT intervention arm - 3 months of HBOT treatment, 9 months observation all participants receive HBOT treatment for 3 months at year 2
    Other Names:
  • Hyperbaric oxygen therapy
  • Device: Sham intervention
    Sham was selected as the control condition rather than "usual care" to equate intervention groups with respect to other variables that could influence cognition and functional status, such as a new challenge (completing an activity program), peer socialization, and attention from staff.

    Outcome Measures

    Primary Outcome Measures

    1. Change in Cognitive outcome [baseline and 12 months]

      A balanced composite sum of z-scores of 4 executive function tests: (For Trails B, subjects draw lines connecting alternating numbers and letters; for Mazes, subjects draw lines from start to finish in mazes of increasing complexity; for Digit-Symbol, numbers and abstract symbols are paired in a legend, and subjects fill in the symbols for a series of numbers; and Category Fluency totals words for two categories, animals, and for fruit and vegetables. ) And 4 episodic memory tests (immediate and delayed recall - ADAS word list- Subjects read aloud 10 unrelated words on printed cards, and are asked to immediately recall as many as possible, in three learning trials. Delayed recall tests recall of the 10 words, after 15 minutes. Logical Memory subtest of the Wechsler Memory Scale-III is a paragraph recall test. The 1st story for immediate recall and for delayed recall, 15 minutes later will be used.)

    Secondary Outcome Measures

    1. Change in secondary cognitive outcomes [baseline and 12 months]

      The sum z-scores for 3 computer-based tests (not language dependent), developed through NIH; EXAMINER assessing executive abilities: http://examiner.ucsf.edu).

    2. CDR-SB [baseline and 12 months]

      Clinical Dementia Rating-Sum of Boxes (CDR-SB), which summarizes impairment in 6 domains (memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care) based on subject and informant interviews. Scores in each of these are combined to obtain a composite score ranging from 0 (no symptoms of dementia) through 3 (severe symptoms of dementia).

    3. ADL questionnaire [baseline and 12 months]

      The Barthel scale or Barthel ADL index used to measure performance in ADL with scoring from 0-20. A higher number is associated with a greater likelihood of being able to live at home with a degree of independence following discharge from hospital.

    4. IADL questionnaire [baseline and 12 months]

      The Lawton instrumental activities of daily living scale contains 8 items, with a summary score from 0 (low function) to 8 (high function).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    65 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Diagnosis of T2D

    • Diagnosis of MCI

    • the age of 65

    • Hebrew fluency

    • An informant

    Exclusion Criteria:
    • Brain disease that affects cognition (e.g. Parkinson's disease, schizophrenia).

    • Stroke

    • Epilepsy

    • Chest pathology incompatible with HBOT

    • Inner ear disease

    • Claustrophobia

    • Cholinesterase inhibitors

    • Subjects with an indication for HBOT

    • Counter-indication for MRI or PET

    • Individuals with severe cataracts must have cataract operations before enrolling in the study

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Icahn School of Medicine at Mount Sinai New York New York United States 10029
    2 University of Wisconsin Madison Wisconsin United States 53076
    3 Sheba Medical Center Ramat Gan Israel
    4 Assaf HaRofeh Medical Center Tzrifin Israel 70300

    Sponsors and Collaborators

    • Icahn School of Medicine at Mount Sinai
    • Sheba Medical Center
    • Assaf-Harofeh Medical Center
    • University of Wisconsin, Madison

    Investigators

    • Principal Investigator: Michal Schnaider-Beeri, PhD, Icahn School of Medicine at Mount Sinai
    • Principal Investigator: Mary Sano, PhD, Icahn School of Medicine at Mount Sinai

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Michal Beeri, Professor, Psychiatry, Icahn School of Medicine at Mount Sinai
    ClinicalTrials.gov Identifier:
    NCT03036254
    Other Study ID Numbers:
    • GCO 15-0192
    First Posted:
    Jan 30, 2017
    Last Update Posted:
    Apr 8, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    Yes
    Keywords provided by Michal Beeri, Professor, Psychiatry, Icahn School of Medicine at Mount Sinai
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Apr 8, 2022