Mechanisms of Impaired Brain Blood Flow With Aging

Sponsor

University of Delaware (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03775382

Collaborator

(none)

Enrollment

Location

Arms

46.1

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Aging is the primary risk factor for Alzheimer's disease (AD), which is a rapidly growing public health concern. Understanding the mechanisms of normal brain aging may provide insight into the factors linking advancing age to increased risk for AD and thereby lead to new therapeutic targets for preventing or slowing AD progression. Cardiovascular changes, including impaired cerebrovascular function, occur with aging and may increase risk for AD; however, the mechanisms by which cerebrovascular function becomes impaired in older adults are incompletely understood. The overall goal of this project is to examine potential mechanisms of age-related declines in cerebrovascular function in humans. The investigators hypothesize that brain macro-vascular endothelial dysfunction, secondary to oxidative stress, plays an important role in mediating age-related changes in brain blood flow and cerebrovascular reactivity. The results of this pilot study have the potential to identify novel targets of cerebrovascular aging and will help guide the design of future clinical trials aimed at improving cerebral blood flow in older adults.

Condition or Disease	Intervention/Treatment	Phase
Aging	Other: Ascorbic Acid Other: Normal Saline	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

34 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

Mechanisms of Impaired Brain Blood Flow With Aging

Actual Study Start Date :

Oct 30, 2017

Anticipated Primary Completion Date :

Sep 1, 2021

Anticipated Study Completion Date :

Sep 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Normal saline will be infused by the research nurse into an antecubital vein using an IV infusion pump.	Other: Normal Saline Normal saline will be infused by the research nurse into an antecubital vein using an IV infusion pump.
Active Comparator: Ascorbic Acid Ascorbic acid will be measured into sterile syringes by the research nurse and infused into an antecubital vein using a IV infusion pump beginning with a priming bolus of 0.06 g Ascorbic Acid per kg fat-free mass dissolved in 100 ml of saline or lactated ringers followed by a "drip-infusion" of 0.02 g Ascorbic Acid per kg fat-free mass dissolved in 30 ml of saline.	Other: Ascorbic Acid Ascorbic acid will be infused into an antecubital vein using a IV infusion pump beginning with a priming bolus of 0.06 g Ascorbic Acid per kg fat-free mass dissolved in 100 ml of saline followed by a "drip-infusion" of 0.02 g Ascorbic Acid per kg fat-free mass dissolved in 30 ml of saline. Other Names: Vitamin C

Arm

Intervention/Treatment

Placebo Comparator: Placebo

Normal saline will be infused by the research nurse into an antecubital vein using an IV infusion pump.

Other: Normal Saline

Normal saline will be infused by the research nurse into an antecubital vein using an IV infusion pump.

Active Comparator: Ascorbic Acid

Ascorbic acid will be measured into sterile syringes by the research nurse and infused into an antecubital vein using a IV infusion pump beginning with a priming bolus of 0.06 g Ascorbic Acid per kg fat-free mass dissolved in 100 ml of saline or lactated ringers followed by a "drip-infusion" of 0.02 g Ascorbic Acid per kg fat-free mass dissolved in 30 ml of saline.

Other: Ascorbic Acid

Ascorbic acid will be infused into an antecubital vein using a IV infusion pump beginning with a priming bolus of 0.06 g Ascorbic Acid per kg fat-free mass dissolved in 100 ml of saline followed by a "drip-infusion" of 0.02 g Ascorbic Acid per kg fat-free mass dissolved in 30 ml of saline.

Other Names:

Vitamin C

Outcome Measures

Primary Outcome Measures

Change from baseline in internal carotid artery (ICA) diameter after acute infusion of the antioxidant ascorbic acid [Change from baseline to 30 minutes post-infusion]
Cerebrovascular reactivity to hypercapnia

Secondary Outcome Measures

Change from baseline in middle cerebral artery (MCA) diameter after acute infusion of the antioxidant ascorbic acid [Change from baseline to 30 minutes post-infusion]
Cerebrovascular reactivity to hypercapnia

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 79 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

18-29 or 55-79 years old

Exclusion Criteria:

Pregnancy or breastfeeding;
Blood chemistries indicative of abnormal renal, liver, thyroid and adrenal function (i.e., outside of normal reference range); estimated glomerular filtration rate using the MDRD prediction equation must be >60 ml/min/1.73 m2;
Abnormal blood chemistry that is clinically relevant or any blood chemistry marker that is +/-2.5x the upper or lower limit;
Lack of a suitable temporal window for cerebrovascular assessments;
Current smoking;
Chronic clinical diseases (e.g., coronary artery, peripheral artery, or cerebrovascular diseases, diabetes, chronic kidney disease, COPD);
Major psychiatric disorder (e.g. Alzheimer's disease or other form of dementia, schizophrenia, bipolar disorder, major depression within past two years);
Neurological or autoimmune conditions affecting cognition (e.g. Parkinson's disease, epilepsy, multiple sclerosis, head trauma with loss of consciousness greater than 30 min, large vessel infarct);
Current medication use likely to affect CNS functions (e.g. long active benzodiazepines);
Having past or present alcohol dependence or abuse, as defined by the American Psychiatry Association, Diagnostic and Statistical Manual of Mental Disorders;
Body mass index (BMI) >40 kg/m2 (FMD measurements can be inaccurate in severely obese patients).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Neurovascular Aging Laboratory	Newark	Delaware	United States	19713

Sponsors and Collaborators

University of Delaware

Investigators

Principal Investigator: Christopher R Martens, Ph.D., University of Delaware

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Christopher Martens, Assistant Professor, University of Delaware

ClinicalTrials.gov Identifier:

NCT03775382

Other Study ID Numbers:

Martens - 1138735

First Posted:

Dec 13, 2018

Last Update Posted:

Apr 2, 2021

Last Verified:

Mar 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Ascorbic Acid

Study Results

No Results Posted as of Apr 2, 2021