HealthyNCT02840851
Brain Blood Flow: Age and Gender
An observational study of Healthy and Aging, run by University of Wisconsin, Madison at 1 site in United States.
Trial summary
Baseline cerebral blood flow through the middle cerebral artery (MCA) and cerebral vasodilator response of the MCA to inhaled carbon dioxide (CO2) will be measured in young women, young men, older women, and older men using Magnetic Resonance (MR) imaging and transcranial Doppler ultrasound (TCD). Read more about this study
- Who is it for?
- Ages 20 to 64 yearsHealthy volunteers can take part
- What is being tested?
- MRI and TCD
- Type of treatment
- Medical device
- How many people
- 46 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2016to Sep 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 64 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: Subjects for this study will include healthy young adults (20-34 years old) and healthy older adults (50-69 years old). Both men and women will be eligible to participate in this study.
Who may be able to join
- Between 20-34 or 50-69 years
- Body mass index <34 kg/m2
Who cannot join
- Current smoker
- History or evidence of: hepatic disease, renal disease, hematological disease, peripheral vascular disease, stroke/neurovascular disease, diabetes, hypertension
- Part of a vulnerable population (e.g. pregnant women, prisoner, individuals lacking capacity to consent, etc.)
- Older females only: subject is not post-menopausal
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Wisconsin-Madison
Madison, Wisconsin, 53706
About this study
Official title: Brain Blood Flow Response to Hypercapnia in Healthy Adults: The Effect of Age and Sex
Baseline cerebral blood flow through the middle cerebral artery (MCA) and cerebral vasodilator response of the MCA to inhaled carbon dioxide (CO2) will be measured in young women, young men, older women, and older men using Magnetic Resonance (MR) imaging and transcranial Doppler ultrasound (TCD). Data collection techniques will be compared.
Read the detailed description
The investigators have recently shown that cerebral blood flow responses to chemical stimuli are reduced in healthy older adults. The investigators also have preliminary data suggesting that sex differences in cerebrovascular regulation exist. The overall goal of this application is to extend on the investigators previous studies by employing advanced neuroimaging techniques to enhance the investigators understanding of neurovascular coupling in healthy aging. This study will collect clinically significant data with implications for the future risk of cognitive decline and Alzheimer's disease.
The research aims are:
- To determine the effect of age and sex on baseline cerebral blood flow through the middle cerebral artery (MCA).
- To determine the effect of age and sex on cerebral vasodilator responses.
- To determine if the cerebrovascular responses measured by transcranial Doppler ultrasound (TCD) are associated with the cerebrovascular responses measured by Magnetic Resonance (MR) imaging.
- Being tested
- MRI, TCD
- Keywords
- Magnetic Resonance Imaging, Transcranial Doppler Ultrasound, Hypercapnia
- Medical subject headings
- Hypercapnia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRIDevice
Also called Magnetic Resonance Imaging
Participants will undergo a MRI scan while two stepwise CO2 elevations are applied to the participant by adding fractional concentration of inspired CO2 (FICO2) at 4% and 6% each time. The end tidal CO2 (PetCO2) will be elevated and maintained constant for a few minutes at each target level. Breath-by-breath changes in respiratory rate and PetCO2 will be measured.
TCDDevice
Also called Transcranial Doppler Ultrasound
Participants will undergo a TCD scan while two stepwise CO2 elevations are applied to the participant by adding fractional concentration of inspired CO2 (FICO2) at 4% and 6% each time. The end tidal CO2 (PetCO2) will be elevated and maintained constant for a few minutes at each target level. Breath-by-breath changes in respiratory and PetCO2 will be measured.
| Study group | Role | What they receive |
|---|---|---|
| Healthy young women | Healthy young women between the age of 20-34 years. Receives: Device: MRI; Device: TCD | |
| Healthy young men | Healthy young men between the age of 20-34 years. Receives: Device: MRI; Device: TCD | |
| Healthy older women | Healthy older women between the age of 50-64 years. Receives: Device: MRI; Device: TCD | |
| Healthy older men | Healthy older men between the age of 50-64 years. Receives: Device: MRI; Device: TCD |
What is being measured
The primary outcome is the main question the study is designed to answer.
Middle Cerebral Artery Blood Flow Measurement
Utilize the TCD and MR imaging to measure middle cerebral artery blood flow in the brain while the participant is at rest.
Measured: 75 minutes
Middle Cerebral Artery Blood Flow Reactivity to Hypercapnia
Utilize the TCD and MR imaging to measure middle cerebral artery blood flow reactivity to hypercapnic gas.
Measured: 75 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2016 (estimated)
- Study startNov 2016
- Primary completionSep 2018
- Study completionSep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (20)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jill N Barnes, PhD, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02840851
- Sponsor's protocol ID
- 2016-0403
- Other IDs
- A176000, EDUC/KINESIOLOGY/KINESIO
- Status last verified
- Dec 2019
- First submitted
- 19 Jul 2016
- Last updated
- 9 Dec 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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. doi: 10.1152/japplphysiol.00966.2005.
PubMed 16357086Bakker 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. doi: 10.1159/000078503.
PubMed 15272220Selim 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.
PubMed 18726054Dandona 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. doi: 10.1136/bmj.2.6133.325.
PubMed 687900Barnes 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.
PubMed 22442028Lipsitz 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. doi: 10.1161/01.str.31.8.1897.
PubMed 10926954Kearney-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.
PubMed 19246701Smith 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.
PubMed 19443808Celermajer 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. doi: 10.1016/0735-1097(94)90141-4.
PubMed 7930277Panza 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. doi: 10.1056/NEJM199007053230105.
PubMed 2355955Kugiyama 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. doi: 10.1038/344160a0.
PubMed 2106627Luscher TF, Diederich D, Siebenmann R, Lehmann K, Stulz P, von Segesser L, Yang ZH, Turina M, Gradel 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. doi: 10.1056/NEJM198808253190802.
PubMed 3136329Mitchell GF, van Buchem MA, Sigurdsson S, Gotal JD, Jonsdottir MK, Kjartansson O, 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.
PubMed 22075523Ide 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. doi: 10.1152/japplphysiol.01186.2002.
PubMed 19278048Ivancev 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.
PubMed 19442931
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Brain Blood Flow Response to Hypercapnia in Healthy Adults: The Effect of Age and Sex
- ClinicalTrials.gov ID
- NCT02840851
- Acronym / sponsor ID
- 2016-0403
- Keywords
- Magnetic Resonance Imaging, Transcranial Doppler Ultrasound, Hypercapnia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Study start
- Nov 2016 (actual)
- Primary completion
- Sep 2018 (actual)
- Study completion
- Sep 2018 (actual)
- First posted
- 21 Jul 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Baseline cerebral blood flow through the middle cerebral artery (MCA) and cerebral vasodilator response of the MCA to inhaled carbon dioxide (CO2) will be measured in young women, young men, older women, and older men using Magnetic Resonance (MR) imaging and transcranial Doppler ultrasound (TCD). Data collection techniques will be compared.
Detailed description
The investigators have recently shown that cerebral blood flow responses to chemical stimuli are reduced in healthy older adults. The investigators also have preliminary data suggesting that sex differences in cerebrovascular regulation exist. The overall goal of this application is to extend on the investigators previous studies by employing advanced neuroimaging techniques to enhance the investigators understanding of neurovascular coupling in healthy aging. This study will collect clinically significant data with implications for the future risk of cognitive decline and Alzheimer's disease.
The research aims are:
- To determine the effect of age and sex on baseline cerebral blood flow through the middle cerebral artery (MCA).
- To determine the effect of age and sex on cerebral vasodilator responses.
- To determine if the cerebrovascular responses measured by transcranial Doppler ultrasound (TCD) are associated with the cerebrovascular responses measured by Magnetic Resonance (MR) imaging.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Healthy young women | – | Device: MRI, Device: TCDHealthy young women between the age of 20-34 years. |
| Healthy young men | – | Device: MRI, Device: TCDHealthy young men between the age of 20-34 years. |
| Healthy older women | – | Device: MRI, Device: TCDHealthy older women between the age of 50-64 years. |
| Healthy older men | – | Device: MRI, Device: TCDHealthy older men between the age of 50-64 years. |
Who may qualify
- Ages
- 20 to 64 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Subjects for this study will include healthy young adults (20-34 years old) and healthy older adults (50-69 years old). Both men and women will be eligible to participate in this study.
Key inclusion criteria (2 listed)
- Between 20-34 or 50-69 years
- Body mass index <34 kg/m2
Key exclusion criteria (4 listed)
- Current smoker
- History or evidence of: hepatic disease, renal disease, hematological disease, peripheral vascular disease, stroke/neurovascular disease, diabetes, hypertension
- Part of a vulnerable population (e.g. pregnant women, prisoner, individuals lacking capacity to consent, etc.)
- Older females only: subject is not post-menopausal
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MRIAlso: Magnetic Resonance ImagingParticipants will undergo a MRI scan while two stepwise CO2 elevations are applied to the participant by adding fractional concentration of inspired CO2 (FICO2) at 4% and 6% each time. The end tidal CO2 (PetCO2) will be elevated and maintained constant for a few minutes at each target level. Breath-by-breath changes in respiratory rate and PetCO2 will be measured. | Device | Healthy older men, Healthy older women, Healthy young men, Healthy young women |
| TCDAlso: Transcranial Doppler UltrasoundParticipants will undergo a TCD scan while two stepwise CO2 elevations are applied to the participant by adding fractional concentration of inspired CO2 (FICO2) at 4% and 6% each time. The end tidal CO2 (PetCO2) will be elevated and maintained constant for a few minutes at each target level. Breath-by-breath changes in respiratory and PetCO2 will be measured. | Device | Healthy older men, Healthy older women, Healthy young men, Healthy young women |
Primary outcome
Middle Cerebral Artery Blood Flow Measurement
Time frame: 75 minutes
Utilize the TCD and MR imaging to measure middle cerebral artery blood flow in the brain while the participant is at rest.
Middle Cerebral Artery Blood Flow Reactivity to Hypercapnia
Time frame: 75 minutes
Utilize the TCD and MR imaging to measure middle cerebral artery blood flow reactivity to hypercapnic gas.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2019.
- Background: PubMed 16357086Girouard 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. doi: 10.1152/japplphysiol.00966.2005.
- Background: PubMed 15272220Bakker 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. doi: 10.1159/000078503.
- Background: PubMed 18726054Selim 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.
- Background: PubMed 687900Dandona 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. doi: 10.1136/bmj.2.6133.325.
- Background: PubMed 22442028Barnes 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.
- Background: PubMed 10926954Lipsitz 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. doi: 10.1161/01.str.31.8.1897.
- Background: PubMed 19246701Kearney-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.
- Background: PubMed 19443808Smith 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.
- Background: PubMed 7930277Celermajer 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. doi: 10.1016/0735-1097(94)90141-4.
- Background: PubMed 2355955Panza 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. doi: 10.1056/NEJM199007053230105.
- Background: PubMed 2106627Kugiyama 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. doi: 10.1038/344160a0.
- Background: PubMed 3136329Luscher TF, Diederich D, Siebenmann R, Lehmann K, Stulz P, von Segesser L, Yang ZH, Turina M, Gradel 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. doi: 10.1056/NEJM198808253190802.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jill N Barnes, PhD principal investigator
University of Wisconsin, Madison
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Healthy and Aging, run by University of Wisconsin, Madison at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Middle Cerebral Artery Blood Flow Measurement (time frame: 75 minutes). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02840851, which also lists 20 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2019.