search
Back to results

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

Primary Purpose

Diabetes Mellitus

Status
Recruiting
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
HBOT intervention
Sham intervention
Sponsored by
Icahn School of Medicine at Mount Sinai
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus focused on measuring Diabetes Mellitus, Cognition

Eligibility Criteria

65 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Icahn School of Medicine at Mount SinaiRecruiting
  • University of WisconsinRecruiting
  • Sheba Medical CenterRecruiting
  • Assaf HaRofeh Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

HBOT intervention

Sham intervention

Arm Description

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.

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.).

Outcomes

Primary Outcome Measures

Change in Cognitive outcome
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

Change in secondary cognitive outcomes
The sum z-scores for 3 computer-based tests (not language dependent), developed through NIH; EXAMINER assessing executive abilities: http://examiner.ucsf.edu).
CDR-SB
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).
ADL questionnaire
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.
IADL questionnaire
The Lawton instrumental activities of daily living scale contains 8 items, with a summary score from 0 (low function) to 8 (high function).

Full Information

First Posted
January 25, 2017
Last Updated
March 8, 2023
Sponsor
Icahn School of Medicine at Mount Sinai
Collaborators
Sheba Medical Center, Assaf-Harofeh Medical Center, University of Wisconsin, Madison
search

1. Study Identification

Unique Protocol Identification Number
NCT03036254
Brief Title
Hyperbaric Oxygen Therapy for Cognition in Diabetic Elderly at High Dementia Risk
Official Title
Hyperbaric Oxygen Therapy for Cognition in Diabetic Elderly at High Dementia Risk
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 8, 2017 (Actual)
Primary Completion Date
May 2024 (Anticipated)
Study Completion Date
May 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Icahn School of Medicine at Mount Sinai
Collaborators
Sheba Medical Center, Assaf-Harofeh Medical Center, University of Wisconsin, Madison

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus
Keywords
Diabetes Mellitus, Cognition

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
154 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
HBOT intervention
Arm Type
Experimental
Arm Description
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.
Arm Title
Sham intervention
Arm Type
Sham Comparator
Arm Description
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.).
Intervention Type
Device
Intervention Name(s)
HBOT intervention
Other Intervention Name(s)
Hyperbaric oxygen therapy
Intervention Description
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
Intervention Type
Device
Intervention Name(s)
Sham intervention
Intervention Description
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 Measure Information:
Title
Change in Cognitive outcome
Description
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.)
Time Frame
baseline and 12 months
Secondary Outcome Measure Information:
Title
Change in secondary cognitive outcomes
Description
The sum z-scores for 3 computer-based tests (not language dependent), developed through NIH; EXAMINER assessing executive abilities: http://examiner.ucsf.edu).
Time Frame
baseline and 12 months
Title
CDR-SB
Description
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).
Time Frame
baseline and 12 months
Title
ADL questionnaire
Description
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.
Time Frame
baseline and 12 months
Title
IADL questionnaire
Description
The Lawton instrumental activities of daily living scale contains 8 items, with a summary score from 0 (low function) to 8 (high function).
Time Frame
baseline and 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Michal Schnaider-Beeri, PhD
Phone
212-659-8807
Email
michal.beeri@mssm.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Ori Benari, M.Sc
Phone
(778) 382-7546
Email
Ori.BenAri@sheba.health.gov.il
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michal Schnaider-Beeri, PhD
Organizational Affiliation
Icahn School of Medicine at Mount Sinai
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Mary Sano, PhD
Organizational Affiliation
Icahn School of Medicine at Mount Sinai
Official's Role
Principal Investigator
Facility Information:
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rebecca West, PhD
Phone
212-659-5603
Email
rebecca.west@mssm.edu
First Name & Middle Initial & Last Name & Degree
Michal Schnaider-Beeri, PhD
Phone
212-659-8807
Email
michal.beeri@mssm.edu
First Name & Middle Initial & Last Name & Degree
Michal Schnaider-Beeri, PhD
Facility Name
University of Wisconsin
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53076
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Barbara Bendlin, PhD
Phone
608-265-2483
Email
bbb@medicine.wisc.edu
First Name & Middle Initial & Last Name & Degree
Jennifer Oh, M.A.
Phone
(608)265-9161
Email
jmoh@medicine.wisc.edu
First Name & Middle Initial & Last Name & Degree
Barbara Bendlin, PhD
Facility Name
Sheba Medical Center
City
Ramat Gan
Country
Israel
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ramit Ravona, PhD
Phone
972-3-5303825
Email
ramitrs@hotmail.com
First Name & Middle Initial & Last Name & Degree
Keren Koifman, BA
Email
Keren.Koifman@sheba.health.gov.il
First Name & Middle Initial & Last Name & Degree
Ramit Ravona, PhD
Facility Name
Assaf HaRofeh Medical Center
City
Tzrifin
ZIP/Postal Code
70300
Country
Israel
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shai Efrati, MD
Phone
972-(0)8-977-9393/5
Email
efratishai@013.net
First Name & Middle Initial & Last Name & Degree
Osha Meir, BA
Phone
972-8-9779393
First Name & Middle Initial & Last Name & Degree
Shai Efrati, MD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.

Learn more about this trial

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

We'll reach out to this number within 24 hrs