Cerebrovascular Circulation Clinical Trial
Official title:
Cerebral Vasodilator Responses in Sedentary and Exercise Trained Humans
Verified date | December 2019 |
Source | University of Wisconsin, Madison |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Cerebral vasodilator responses to CO2 will be measured in young healthy adults, healthy sedentary older adults, and healthy exercise trained older adults. This variable will be examined before and after administering the cyclooxygenase inhibitor indomethacin, which has been shown to blunt cerebral vasodilator responses. In addition, the investigators will examine these counter-regulatory hemodynamic mechanisms to hypoperfusion caused by indomethacin.
Status | Completed |
Enrollment | 80 |
Est. completion date | April 2019 |
Est. primary completion date | April 2019 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 75 Years |
Eligibility |
Inclusion Criteria: - Young subjects between 18-35 years old - Older subjects between 55-75 years old - Nonsmokers - Physically active (exercise more than 3 times per week for at least 30 minutes) - Sedentary (no formal exercise over 1 hour per week). Exclusion Criteria: - Outside of the specified age range - Present with history or evidence of hepatic, renal, or hematological disease; peripheral vascular disease; stroke/neurovascular disease; diabetes; hypertension - Take medications that indicate hepatic, renal, hematological disease; cardiovascular disease, including hypertension; stroke/neurovascular disease; and diabetes - Body mass index >34 kg/m2 - Take physician-prescribed medications that may interact with indomethacin: 1) cardiovascular drugs (e.g. angiotensin-converting-enzyme inhibitor (ACE inhibitors), angiotensin II receptor blockers (ARB's), Diuretics); 2) drugs that would increase bleeding risk (e.g. warfarin, heparin, clopidogrel, rivaroxaban, other NSAIDs); or 3) drugs associated with increased renal toxicity (e.g. cyclosporin, tacrolimus) - Vulnerable populations (i.e. pregnant women, prisoners, individuals lacking capacity to consent, etc.) |
Country | Name | City | State |
---|---|---|---|
United States | Gymnasium-Natatorium | Madison | Wisconsin |
Lead Sponsor | Collaborator |
---|---|
University of Wisconsin, Madison | National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH) |
United States,
Ainslie PN, Cotter JD, George KP, Lucas S, Murrell C, Shave R, Thomas KN, Williams MJ, Atkinson G. Elevation in cerebral blood flow velocity with aerobic fitness throughout healthy human ageing. J Physiol. 2008 Aug 15;586(16):4005-10. doi: 10.1113/jphysiol.2008.158279. Epub 2008 Jul 17. — View Citation
Andrews-Hanna JR, Snyder AZ, Vincent JL, Lustig C, Head D, Raichle ME, Buckner RL. Disruption of large-scale brain systems in advanced aging. Neuron. 2007 Dec 6;56(5):924-35. — View Citation
Baker LD, Frank LL, Foster-Schubert K, Green PS, Wilkinson CW, McTiernan A, Cholerton BA, Plymate SR, Fishel MA, Watson GS, Duncan GE, Mehta PD, Craft S. Aerobic exercise improves cognition for older adults with glucose intolerance, a risk factor for Alzheimer's disease. J Alzheimers Dis. 2010;22(2):569-79. doi: 10.3233/JAD-2010-100768. — View Citation
Bakker SL, de Leeuw FE, den Heijer T, Koudstaal PJ, Hofman A, Breteler MM. Cerebral haemodynamics in the elderly: the rotterdam study. Neuroepidemiology. 2004 Jul-Aug;23(4):178-84. — View Citation
Barnes JN, Schmidt JE, Nicholson WT, Joyner MJ. Cyclooxygenase inhibition abolishes age-related differences in cerebral vasodilator responses to hypercapnia. J Appl Physiol (1985). 2012 Jun;112(11):1884-90. doi: 10.1152/japplphysiol.01270.2011. Epub 2012 Mar 22. — View Citation
Carlsson I, Wennmalm A. Effect of different prostaglandin synthesis inhibitors on post-occlusive blood flow in human forearm. Prostaglandins. 1983 Aug;26(2):241-52. — View Citation
Celermajer DS, Sorensen KE, Bull C, Robinson J, Deanfield JE. Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction. J Am Coll Cardiol. 1994 Nov 15;24(6):1468-74. — View Citation
Damoiseaux JS, Beckmann CF, Arigita EJ, Barkhof F, Scheltens P, Stam CJ, Smith SM, Rombouts SA. Reduced resting-state brain activity in the "default network" in normal aging. Cereb Cortex. 2008 Aug;18(8):1856-64. Epub 2007 Dec 5. — View Citation
Dandona P, James IM, Newbury PA, Woollard ML, Beckett AG. Cerebral blood flow in diabetes mellitus: evidence of abnormal cerebrovascular reactivity. Br Med J. 1978 Jul 29;2(6133):325-6. — View Citation
DeSouza CA, Shapiro LF, Clevenger CM, Dinenno FA, Monahan KD, Tanaka H, Seals DR. Regular aerobic exercise prevents and restores age-related declines in endothelium-dependent vasodilation in healthy men. Circulation. 2000 Sep 19;102(12):1351-7. — View Citation
Droste DW, Harders AG, Rastogi E. A transcranial Doppler study of blood flow velocity in the middle cerebral arteries performed at rest and during mental activities. Stroke. 1989 Aug;20(8):1005-11. — View Citation
Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A, Chaddock L, Kim JS, Heo S, Alves H, White SM, Wojcicki TR, Mailey E, Vieira VJ, Martin SA, Pence BD, Woods JA, McAuley E, Kramer AF. Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):3017-22. doi: 10.1073/pnas.1015950108. Epub 2011 Jan 31. — View Citation
Franzoni F, Ghiadoni L, Galetta F, Plantinga Y, Lubrano V, Huang Y, Salvetti G, Regoli F, Taddei S, Santoro G, Salvetti A. Physical activity, plasma antioxidant capacity, and endothelium-dependent vasodilation in young and older men. Am J Hypertens. 2005 Apr;18(4 Pt 1):510-6. — View Citation
Frauenfelder BA, Schuepbach D, Baumgartner RW, Hell D. Specific alterations of cerebral hemodynamics during a planning task: a transcranial Doppler sonography study. Neuroimage. 2004 Jul;22(3):1223-30. — View Citation
Galetta F, Franzoni F, Plantinga Y, Ghiadoni L, Rossi M, Prattichizzo F, Carpi A, Taddei S, Santoro G. Ambulatory blood pressure monitoring and endothelium-dependent vasodilation in the elderly athletes. Biomed Pharmacother. 2006 Sep;60(8):443-7. Epub 2006 Aug 2. — View Citation
Geda YE, Roberts RO, Knopman DS, Christianson TJ, Pankratz VS, Ivnik RJ, Boeve BF, Tangalos EG, Petersen RC, Rocca WA. Physical exercise, aging, and mild cognitive impairment: a population-based study. Arch Neurol. 2010 Jan;67(1):80-6. doi: 10.1001/archneurol.2009.297. — View Citation
Girouard H, Iadecola C. Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease. J Appl Physiol (1985). 2006 Jan;100(1):328-35. Review. — View Citation
Green DJ, O'Driscoll G, Joyner MJ, Cable NT. Exercise and cardiovascular risk reduction: time to update the rationale for exercise? J Appl Physiol (1985). 2008 Aug;105(2):766-8. doi: 10.1152/japplphysiol.01028.2007. Epub 2008 Jan 3. — View Citation
Ide K, Eliasziw M, Poulin MJ. Relationship between middle cerebral artery blood velocity and end-tidal PCO2 in the hypocapnic-hypercapnic range in humans. J Appl Physiol (1985). 2003 Jul;95(1):129-37. — View Citation
Ivancev V, Bakovic D, Obad A, Breskovic T, Palada I, Joyner MJ, Dujic Z. Effects of indomethacin on cerebrovascular response to hypercapnea and hypocapnea in breath-hold diving and obstructive sleep apnea. Respir Physiol Neurobiol. 2009 May 15;166(3):152-8. doi: 10.1016/j.resp.2009.03.001. Epub 2009 Mar 18. — View Citation
Jensen K, Kjaergaard S, Malte E, Bünemann L, Therkelsen K, Knudsen F. Effect of graduated intravenous and standard rectal doses of indomethacin on cerebral blood flow in healthy volunteers. J Neurosurg Anesthesiol. 1996 Apr;8(2):111-6. — View Citation
Kearney-Schwartz A, Rossignol P, Bracard S, Felblinger J, Fay R, Boivin JM, Lecompte T, Lacolley P, Benetos A, Zannad F. Vascular structure and function is correlated to cognitive performance and white matter hyperintensities in older hypertensive patients with subjective memory complaints. Stroke. 2009 Apr;40(4):1229-36. doi: 10.1161/STROKEAHA.108.532853. Epub 2009 Feb 26. — View Citation
Kelley RE, Chang JY, Scheinman NJ, Levin BE, Duncan RC, Lee SC. Transcranial Doppler assessment of cerebral flow velocity during cognitive tasks. Stroke. 1992 Jan;23(1):9-14. — View Citation
Kugiyama K, Kerns SA, Morrisett JD, Roberts R, Henry PD. Impairment of endothelium-dependent arterial relaxation by lysolecithin in modified low-density lipoproteins. Nature. 1990 Mar 8;344(6262):160-2. — View Citation
Lautenschlager NT, Cox KL, Flicker L, Foster JK, van Bockxmeer FM, Xiao J, Greenop KR, Almeida OP. Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial. JAMA. 2008 Sep 3;300(9):1027-37. doi: 10.1001/jama.300.9.1027. Erratum in: JAMA. 2009 Jan 21;301(3):276. — View Citation
Lipsitz LA, Mukai S, Hamner J, Gagnon M, Babikian V. Dynamic regulation of middle cerebral artery blood flow velocity in aging and hypertension. Stroke. 2000 Aug;31(8):1897-903. — View Citation
Lucas SJ, Ainslie PN, Murrell CJ, Thomas KN, Franz EA, Cotter JD. Effect of age on exercise-induced alterations in cognitive executive function: relationship to cerebral perfusion. Exp Gerontol. 2012 Aug;47(8):541-51. doi: 10.1016/j.exger.2011.12.002. Epub 2012 Jan 2. — View Citation
Lüscher TF, Diederich D, Siebenmann R, Lehmann K, Stulz P, von Segesser L, Yang ZH, Turina M, Grädel E, Weber E, et al. Difference between endothelium-dependent relaxation in arterial and in venous coronary bypass grafts. N Engl J Med. 1988 Aug 25;319(8):462-7. — View Citation
MacLeod CM. Half a century of research on the Stroop effect: an integrative review. Psychol Bull. 1991 Mar;109(2):163-203. Review. — View Citation
Mitchell GF, van Buchem MA, Sigurdsson S, Gotal JD, Jonsdottir MK, Kjartansson Ó, Garcia M, Aspelund T, Harris TB, Gudnason V, Launer LJ. Arterial stiffness, pressure and flow pulsatility and brain structure and function: the Age, Gene/Environment Susceptibility--Reykjavik study. Brain. 2011 Nov;134(Pt 11):3398-407. doi: 10.1093/brain/awr253. — View Citation
Owen AM, Downes JJ, Sahakian BJ, Polkey CE, Robbins TW. Planning and spatial working memory following frontal lobe lesions in man. Neuropsychologia. 1990;28(10):1021-34. — View Citation
Panza JA, Quyyumi AA, Brush JE Jr, Epstein SE. Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med. 1990 Jul 5;323(1):22-7. — View Citation
Raz L, Jayachandran M, Tosakulwong N, Lesnick TG, Wille SM, Murphy MC, Senjem ML, Gunter JL, Vemuri P, Jack CR Jr, Miller VM, Kantarci K. Thrombogenic microvesicles and white matter hyperintensities in postmenopausal women. Neurology. 2013 Mar 5;80(10):911-8. doi: 10.1212/WNL.0b013e3182840c9f. Epub 2013 Feb 13. — View Citation
Schuepbach D, Boeker H, Duschek S, Hell D. Rapid cerebral hemodynamic modulation during mental planning and movement execution: evidence of time-locked relationship with complex behavior. Clin Neurophysiol. 2007 Oct;118(10):2254-62. Epub 2007 Sep 4. — View Citation
Seifert T, Brassard P, Wissenberg M, Rasmussen P, Nordby P, Stallknecht B, Adser H, Jakobsen AH, Pilegaard H, Nielsen HB, Secher NH. Endurance training enhances BDNF release from the human brain. Am J Physiol Regul Integr Comp Physiol. 2010 Feb;298(2):R372-7. doi: 10.1152/ajpregu.00525.2009. Epub 2009 Nov 18. — View Citation
Selim M, Jones R, Novak P, Zhao P, Novak V. The effects of body mass index on cerebral blood flow velocity. Clin Auton Res. 2008 Dec;18(6):331-8. doi: 10.1007/s10286-008-0490-z. Epub 2008 Aug 22. — View Citation
Serrador JM, Picot PA, Rutt BK, Shoemaker JK, Bondar RL. MRI measures of middle cerebral artery diameter in conscious humans during simulated orthostasis. Stroke. 2000 Jul;31(7):1672-8. — View Citation
Smith EE, Greenberg SM. Beta-amyloid, blood vessels, and brain function. Stroke. 2009 Jul;40(7):2601-6. doi: 10.1161/STROKEAHA.108.536839. Epub 2009 May 14. Review. — View Citation
Taddei S, Virdis A, Ghiadoni L, Versari D, Salvetti A. Which endothelium-derived factors are really important in humans? Biol Chem. 2006 Feb;387(2):151-7. Review. — View Citation
Taddei S, Virdis A, Mattei P, Ghiadoni L, Gennari A, Fasolo CB, Sudano I, Salvetti A. Aging and endothelial function in normotensive subjects and patients with essential hypertension. Circulation. 1995 Apr 1;91(7):1981-7. — View Citation
Xie A, Skatrud JB, Morgan B, Chenuel B, Khayat R, Reichmuth K, Lin J, Dempsey JA. Influence of cerebrovascular function on the hypercapnic ventilatory response in healthy humans. J Physiol. 2006 Nov 15;577(Pt 1):319-29. Epub 2006 Aug 24. — View Citation
* Note: There are 41 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Cerebral Vasodilator Responses | Utilize a Transcranial Doppler to measure blood flow velocity in response to inhaled carbon dioxide. | Measurement at baseline | |
Secondary | Cerebral Vasodilator Responses | Utilize a Transcranial Doppler to measure blood flow velocity in response to inhaled carbon dioxide. | Measurement beginning 60 minutes post drug and measured through 180 minutes | |
Secondary | Blood Pressure | Measurement at baseline and beginning 60 minutes post drug and measured through 180 minutes |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT03704519 -
Imaging Study to Compare Effects of Darolutamide and Enzalutamide With Respect to Placebo on the Blood Flow in the Brain in Healthy Male Volunteers.
|
Phase 1 | |
Recruiting |
NCT05920759 -
Sex-specific Effect of Restricted Sleep on Brain Health
|
N/A | |
Recruiting |
NCT03512613 -
A Pilot Study- Monitoring Cerebral Blood Flow in Neonates With Congenital Heart Defects
|
||
Recruiting |
NCT05864950 -
Brain Blood Flow Responses During Exercise
|
N/A | |
Completed |
NCT02982122 -
CPPopt Guided Therapy: Assessment of Target Effectiveness
|
N/A | |
Completed |
NCT03732651 -
The Impact of Non-pulsatile Blood Flow on CO2-Reactivity
|
N/A | |
Completed |
NCT03278769 -
Ventilator Settings on Patients With Acute Brain Injury
|
N/A | |
Recruiting |
NCT05893407 -
Brain PERfusion Evaluation by Contrast-Enhanced UltraSound
|
||
Recruiting |
NCT05051397 -
CO2 Modulation in Endovascular Thrombectomy for Acute Ischemic Stroke
|
Phase 2 | |
Completed |
NCT03484104 -
Cerebral Perfusion in Hypothermic Circulatory Arrest
|
||
Completed |
NCT03816072 -
Quantification of Dynamic and Static Cerebral Autoregulation (CA) Under Anaesthesia
|
N/A | |
Terminated |
NCT04234009 -
Lifestyle and Brain Vascular Function
|
N/A | |
Recruiting |
NCT06368635 -
The Cerebral Microcirculation Diseases and Coronary Microcirculation Disease Study
|
||
Recruiting |
NCT05394935 -
The Effects of High-intensity and Moderate-intensity Exercise on Polycystic Ovary Syndrome
|
N/A | |
Completed |
NCT01169662 -
Effects of Dietary Nitrate From Vegetable/Fruit Juice on Cerebral Blood Flow Parameters
|
Phase 4 | |
Recruiting |
NCT03591523 -
Blood Flow Measurement Using Quantitative Magnetic Resonance Angiography and Duplex Sonography
|
||
Not yet recruiting |
NCT04978558 -
NIRS vs TCD for Cerebrovascular Autoregulation During Non-cardiac Surgery
|
||
Recruiting |
NCT04391465 -
Assessment of the Relationship Between Cerebral Blood Flow and Heart Rate
|
N/A | |
Completed |
NCT03953391 -
The Effect of Tea Breaks on Cerebrovascular Perfusion During Desk Work
|
N/A | |
Recruiting |
NCT02748447 -
Automated Adjustment of Inspired Oxygen to Maintaining Regional Cerebral Oxygenation in Preterm Infants on Respiratory Support
|
N/A |