UTLight-transcranial Doppler Assessment of Regional Cerebral Autoregulation

Diabetes Clinical Trial

— UTLight  

Official title:

UTLight-transcranial Doppler Assessment of Regional Cerebral Autoregulation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02178787
• Other study ID #: 2014P-000027
• Status: Completed
• Phase: N/A
• First received: June 27, 2014
• Last updated: November 17, 2015
• Start date: April 2014
• Est. completion date: June 2015

Study information

• Verified date: November 2015
• Source: Beth Israel Deaconess Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 50 Years to 85 Years

Eligibility

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 exclusion criteria - poor insonation window and TCD signal;

18. UT_Light exclusion- poor signal.

Study Design

Observational Model: Case Control, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Diabetes

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Beth Israel Deaconess Medical Center	Ornim Medical Ltd.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cerebral autoregulation measured by TCD and UT-Ox	A regression analysis will be used to determine the relationship between BP and BFV averaged over entire baseline and tilt, or sitting and standing up periods. The slope for regression will be compared between TCD_BFV and UT_BF and UT_Ox	one year	No
Secondary	CO2 vasoreactivity	CO2 reactivity will be measured as the slope of regression between TCD_BFV and CO2 changes during baseline, hyperventilation, and CO2 rebreathing and also between UT_BF or UT_Ox and CO2 changes during these conditions.	one year	No