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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03036254
Recruitment Status : Recruiting
First Posted : January 30, 2017
Last Update Posted : December 5, 2018
Sheba Medical Center
Assaf-Harofeh Medical Center
University of Wisconsin, Madison
Information provided by (Responsible Party):
Icahn School of Medicine at Mount Sinai

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
Diabetes Mellitus Device: HBOT intervention Device: Sham intervention Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : October 8, 2017
Estimated Primary Completion Date : July 2023
Estimated Study Completion Date : July 2023

Resource links provided by the National Library of Medicine

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 above the ambient atmosphere.
Other Name: 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: 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.

Primary Outcome Measures :
  1. Change in Cognitive outcome [ Time Frame: 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 [ Time Frame: baseline and 12 months ]
    The sum z-scores for 3 computer-based tests (not language dependent), developed through NIH; EXAMINER assessing executive abilities:

  2. CDR-SB [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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).

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   65 Years and older   (Older Adult)
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03036254

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Contact: Michal Schnaider-Beeri, PhD 212-659-8807
Contact: Ramit Ravona, PhD 972-3-5303825

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United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Contact: Rebecca West, PhD    212-659-5603   
Contact: Michal Schnaider-Beeri, PhD    212-659-8807   
Principal Investigator: Michal Schnaider-Beeri, PhD         
United States, Wisconsin
University of Wisconsin Not yet recruiting
Madison, Wisconsin, United States, 53076
Contact: Barbara Bendlin, PhD    608-265-2483   
Contact: Jennifer Oh, M.A.    (608)265-9161   
Principal Investigator: Barbara Bendlin, PhD         
Sheba Medical Center Not yet recruiting
Ramat Gan, Israel
Contact: Ramit Ravona, PhD    972-3-5303825   
Contact: Keren Koifman, BA   
Principal Investigator: Ramit Ravona, PhD         
Assaf HaRofeh Medical Center Not yet recruiting
Tzrifin, Israel, 70300
Contact: Shai Efrati, MD    972-(0)8-977-9393/5   
Contact: Osha Meir, BA    972-8-9779393      
Principal Investigator: Shai Efrati, MD         
Sponsors and Collaborators
Icahn School of Medicine at Mount Sinai
Sheba Medical Center
Assaf-Harofeh Medical Center
University of Wisconsin, Madison
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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

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Responsible Party: Icahn School of Medicine at Mount Sinai Identifier: NCT03036254     History of Changes
Other Study ID Numbers: GCO 15-0192
First Posted: January 30, 2017    Key Record Dates
Last Update Posted: December 5, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified MRI and PET scans and cognitive scores will be made available for investigative collaborations. We expect to share these data with a large number of investigators throughout the world.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No

Keywords provided by Icahn School of Medicine at Mount Sinai:
Diabetes Mellitus

Additional relevant MeSH terms:
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Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders