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

NCT ID: NCT03036254

Last Updated: 2025-08-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 155 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-10
• Study Completion Date: 2024-04-15

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.

Conditions

Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

HBOT intervention

Intervention Type: DEVICE

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

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.).

Group Type: SHAM_COMPARATOR

HBOT intervention

Intervention Type: DEVICE

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

Sham intervention

Intervention Type: DEVICE

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.

Interventions

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

Intervention Type: 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.

Intervention Type: DEVICE

Other Intervention Names

Hyperbaric oxygen therapy

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

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sheba Medical Center

OTHER_GOV

Sponsor Role: collaborator

Assaf-Harofeh Medical Center

OTHER_GOV

Sponsor Role: collaborator

University of Wisconsin, Madison

OTHER

Sponsor Role: collaborator

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: lead

Responsible Party

Michal Beeri

Professor, Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michal Schnaider-Beeri, PhD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Mary Sano, PhD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

Icahn School of Medicine at Mount Sinai

New York, New York, United States

University of Wisconsin

Madison, Wisconsin, United States

Sheba Medical Center

Ramat Gan, , Israel

Assaf HaRofeh Medical Center

Tzrifin, , Israel

Countries

United States; Israel

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

GCO 15-0192

Identifier Type: -

Identifier Source: org_study_id