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.|
|ClinicalTrials.gov Identifier: NCT03036254|
Recruitment Status : Recruiting
First Posted : January 30, 2017
Last Update Posted : December 5, 2018
|Condition or disease||Intervention/treatment||Phase|
|Diabetes Mellitus||Device: HBOT intervention Device: Sham intervention||Not Applicable|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||154 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|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|
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.
- 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.)
- 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: http://examiner.ucsf.edu).
- 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).
- 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.
- 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).
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03036254
|Contact: Michal Schnaider-Beeri, PhDfirstname.lastname@example.org|
|Contact: Ramit Ravona, PhDemail@example.com|
|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 firstname.lastname@example.org|
|Contact: Michal Schnaider-Beeri, PhD 212-659-8807 email@example.com|
|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 firstname.lastname@example.org|
|Contact: Jennifer Oh, M.A. (608)265-9161 email@example.com|
|Principal Investigator: Barbara Bendlin, PhD|
|Sheba Medical Center||Not yet recruiting|
|Ramat Gan, Israel|
|Contact: Ramit Ravona, PhD 972-3-5303825 firstname.lastname@example.org|
|Contact: Keren Koifman, BA Keren.Koifman@sheba.health.gov.il|
|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 email@example.com|
|Contact: Osha Meir, BA 972-8-9779393|
|Principal Investigator: Shai Efrati, MD|
|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|