Diabetes
Conditions
Keywords
cerebral blood flow, near infrared spectroscopy, transcranial Doppler, diabetes mellitus, cerebral autoregulation
Brief summary
Cerebral autoregulation (CA) is a complex mechanism that serves the essential and vital purpose of controlling cerebral blood flow and metabolism. A stable and optimal brain blood flow is imperative for normal brain function. Diabetes Mellitus (DM ) is associated with microvascular disease that alters CA and also with autonomic failure that may lead to orthostatic hypotension (OH). These conditions may lead to decreased brain blood flow in upright position. This observational study will compare two technologies that evaluate brain blood flow during standing up and other maneuvers in people with and without type 2 diabetes. These technologies are transcranial Doppler and UTLight technology (CerOx). This study will determine the safety and feasibility of CerOx technology for continuous monitoring of cerebral blood flow.
Detailed description
Cerebral autoregulation (CA) is a complex mechanism that serves the essential and vital purpose of controlling cerebral blood flow and metabolism. A stable and optimal brain blood flow is imperative for normal brain function; therefore normal function of CA is crucial for brain health. Diabetes mellitus (DM) is associated with microvascular disease and abnormal autoregulation, which increases risk for stroke and death. Failure of CA has serious consequences across the lifespan and, in terms of prevalence adverse outcomes related to failing CA are most prominent in the elderly with diabetes. Older diabetic adults often suffer from hypotension or fainting upon standing-up and may have abnormal CA. With abnormal CA, cerebral perfusion and tissue oxygenation declines upon standing up. Abnormalities in perfusion regulation in older people, and particularly those with diabetes may accelerate progression of brain atrophy resulting in cognitive decline, vascular dementia or Alzheimer's disease. UTLight technology (CerOx), provides a new tool for evaluation of regional blood flow and oxygenation in cortical microvasculature, which is lacking in clinical medicine and patient care. UTLight may become a novel tool that would provide an easy and reliable assessment of regional perfusion and CA in specific cortical areas in health and disease that can be widely implemented in outpatient clinics. This is a pilot, observational feasibility study to compare blood flow measurements using UTLight and TCD. Aim 1: To assess the safety and feasibility of UTLight for evaluation of regional cerebral blood flow regulation in the anterior circulation ((ACA) and/or middle cerebral artery (MCA) territories) in 20 non-diabetic adults \>50 yrs old and 40 age-matched adults with type 2 diabetes. Aim 2: To compare the profiles of UTLight blood flow (UT\_BF), regional oximetry (UT\_Ox) and TCD-blood flow velocities (TCD\_BFV) in response to: 1) blood pressure changes induced by the postural change from supine to head-up tilt, and from sitting to standing-up; and 2) vasodilatation and vasoconstriction responses induced by hypercapnia and hypocapnia. The investigators hypothesize that: 1. UT\_BF will accurately track TCD\_BFV in responses in the anterior circulation (ACA and/or MCA territory) to blood pressure changes, hypercapnia and hypocapnia challenges in healthy older people. 2. UT\_BF may be more sensitive to detect abnormalities in regional perfusion in diabetic adults as compared to healthy controls and compared to TCD\_BFV. (UT\_Ox) may provide a new indicator to identify older diabetic adults with brain tissue hypoxia during orthostatic challenges that may be at greater risk of brain damage of cognitive decline that will be derived from a change in tissue oxygenation upon standing up that is not routinely evaluated by TCD. Outcomes: Primary outcome is the sensitivity and specificity of UT\_BF and TCD\_BFV to blood pressure and CO2 challenges, defined as percent change of UT\_BF and TCD\_BFV in response to hypercapnia and hypocapnia challenges. Secondary outcomes are the differences in cerebral blood flow measured by UT\_BF, TCD\_BFV between healthy old and diabetic subjects during postural changes. Third outcomes are differences in UT\_Ox between healthy old and diabetic subjects.
Interventions
None listed
Sponsors
Ornim Medical Ltd.
Beth Israel Deaconess Medical Center
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
Diabetes group: * This group will consist of 40 men and women aged 50-85 years * diagnosed with type 2 DM and * treated with oral agents and/or combinations with insulin for at least one year, * either normotensive \[BP \<135/85 mm Hg and no medical history of hypertension) or hypertensive \[BP \>130/85 mm Hg and/or treated for hypertension\]. Control group: * This group will be non-diabetic (normal fasting blood glucose and HbA1c \< 6.5%). * This group will consist of 20 men and women matched with the diabetes group by age ±5 years, and * subjects will be normotensive \[BP \<130/85 mm Hg and * no medical history of hypertension\] and * hypertensive \[BP \>130/85 mm Hg and/or treated for hypertension\].
Exclusion criteria
Persons with any one of the following conditions will be excluded: 1. type I diabetes; 2. any unstable or acute medical condition; 3. myocardial infarction or major surgery within 6 months; 4. history of a major stroke; 5. dementia (by history) or inability to follow details of the protocol or MMSE \< 20; 6. carotid stenosis \> 80% by medical history, Doppler ultrasound, or MR angiography; 7. hemodynamically significant valvular disease; 8. clinically significant arrhythmias; 9. liver or renal failure or transplant; 10. severe hypertension \[systolic BP \>200 and/or diastolic BP \>110 mm Hg or subjects taking ≥3 antihypertensive medications\]; 11. seizure disorders; 12. malignant tumors; 13. current recreational drug or alcohol abuse; 14. active smoking; 15. morbid obesity (BMI \>40). 16. Women in both groups will be required to be postmenopausal. 17. TCD
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Compare Profiles of TCD-blood Flow Velocities (TCD_BFV). | one year | CO2 reactivity will be measured as the slope of regression between TCD\_BFV and CO2 changes during baseline, hyperventilation, and CO2 re-breathing. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Compare Profiles of UTlight Blood Flow (UT_BF) and Regional Oximetry (UT_Ox). | one year | CO2 reactivity will be measured as the slope of regression between UT\_BF or UT\_Ox and CO2 changes during baseline, hyperventilation, and CO2 re-breathing. |
Countries
United States
Participant flow
Pre-assignment details
Seventy four consented subjects, thirty type 2 diabetics and thirty non-diabetic controls completed the protocol. Screened participants that did not start the study: eleven were found ineligible after signing informed consent, two withdrew consent, one lost to follow up.
Participants by arm
| Arm | Count |
|---|---|
| Type 2 Diabetics Head-up tilt, vasoreactivity, sitting to standing-up | 30 |
| Non-diabetic Controls Head-up tilt, vasoreactivity, sitting to standing-up | 30 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | No TCD window | 3 | 7 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Type 2 Diabetics | Non-diabetic Controls | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 18 Participants | 19 Participants | 37 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 11 Participants | 23 Participants |
| Age, Continuous | 67 years STANDARD_DEVIATION 7.91 | 66.31 years STANDARD_DEVIATION 9.95 | 66.48 years STANDARD_DEVIATION 8.93 |
| Sex: Female, Male Female | 18 Participants | 12 Participants | 30 Participants |
| Sex: Female, Male Male | 12 Participants | 18 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 30 | 2 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
Primary
To Compare Profiles of TCD-blood Flow Velocities (TCD_BFV).
CO2 reactivity will be measured as the slope of regression between TCD\_BFV and CO2 changes during baseline, hyperventilation, and CO2 re-breathing.
Time frame: one year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Type 2 Diabetics | To Compare Profiles of TCD-blood Flow Velocities (TCD_BFV). | 28.23 cm/sec | Standard Error 2.35 |
| Non-diabetic Controls | To Compare Profiles of TCD-blood Flow Velocities (TCD_BFV). | 33.11 cm/sec | Standard Error 1.54 |
Secondary
To Compare Profiles of UTlight Blood Flow (UT_BF) and Regional Oximetry (UT_Ox).
CO2 reactivity will be measured as the slope of regression between UT\_BF or UT\_Ox and CO2 changes during baseline, hyperventilation, and CO2 re-breathing.
Time frame: one year
Population: The data analysis has determined that UT\_BF and UT\_OX signals were not reliable and required further algorithm modification and development during post processing (e.g. raw data signal to noise, signal averaging) that are beyond the scope of the study. Therefore, the results were inconsistent and inconclusive. No results to report.