Retina Microvascular Remodeling and Cognitive Function In Hypertension

Hypertension Clinical Trial

— EYEBRAIN  

Official title:

Retina Microvascular Remodeling and Cognitive Function In Hypertension : Eyebrain

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02701855
• Other study ID #: 14DRM_EYEBRAIN
• Status: Recruiting
• Phase: N/A
• First received: August 4, 2015
• Last updated: March 2, 2016
• Start date: October 2014
• Est. completion date: December 2017

Study information

• Verified date: March 2016
• Source: Institute of Cardiometabolism and Nutrition, France
• Contact: David Rosenbaum, Dr
• Phone: 01 42 17 57 74
• Email: david.rosenbaum[@]psl.aphp.fr
• Is FDA regulated: No
• Health authority: France: Committee for the Protection of PersonnesFrance: Commission nationale de l'informatique et des libertésFrance: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Observational

Clinical Trial Summary

This study aims to determine the relationships between retina micro-vascular remodeling and cognitive function in hypertensive patients.

The study plans to enrol 160 patients (100 patients with mild cognitive impairment -MCI- and 60 without MCI).

Description:

Our project stands on physiopathological and cognitive angles, and is mainly based on the major role of large and small arteries elasticity on cognitive aging. It will benefit from the recent innovative accurate and non invasive techniques such as MRI for central large arteries and adaptative optics for retina arterioles imaging.

Study population is the following:

• 60 patients with hypertension and no MCI,

• 50 patients with hypertension and stable MCI, without dementia

• 50 patients with hypertension and progressive MCI, without dementia

Every patients will perform a medical interview and examination, an MRI (brain + aorta), adaptative optics imaging, a cognitive tests and a blood test.

Primary outcome is to determine the relationships between retina micro-vascular remodeling and cognitive function in this population.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: December 2017
• Est. primary completion date: September 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 65 Years and older

Eligibility

Inclusion Criteria:

1. Aged 65 or more

2. hypertension (BP =140/90 mmHg and/or antihypertensive treatment)

3. Signed informed consent by the patient

4. Sufficient mastery of the French language to perform neuropsychological tests

Exclusion Criteria:

1. Impossibility to visualize the retinal : severe cataract

2. Dementia (defined by MMSE<20)

3. Clinical stroke

4. Severe or resistant Hypertension

5. Hypertension treated with more than 3 different pharmacological classes

6. any other disease that may interfere with the assessment of cognitive disorders (epilepsy, Parkinson's disease, major depression, schizophrenia, manic-depressive)

7. Enrolment in a therapeutic trial that could interfere with the main objective

8. Less than 4 years of formal education

9. Illiterate, unable to read, write or count

10. major physical problems that may interfere with the tests (sight, hearing, ...)

11. Short term life threatening disease

12. Non-affiliation to a healthcare system

13. Consent refusal

14. Contraindication to MRI including claustrophobia, metallic devices, pacemaker, mechanical valve implanted before 1985, and nursing, as well as technical contra-indication: patient diameter > 70 cm or/and weight > 250 kg

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Cognition Disorders
• Hypertension
• Mild Cognitive Impairment

Intervention

Behavioral:
• Cognitive tests
Cognitive tests include: The MMSE (Mini Mental State Examination) Free and Cued Selective Recall Reminding Test (FCSRT). Executive functions (fluencies, TMT A and B, span). Tests of verbal fluency (literal and category) Digit symbol substitution test or Wechsler adult intelligence scale (W.A.I.S) The Clinical Dementia Rating Scale The IADL scale evaluates autonomy. Geriatric Depression screening Scale (GDS)

Biological:
• Blood test
A blood test will be performed in order to collect following parameters: Urea, BUN, Creatinine, Potassium, Sodium, hematocrit, hsCRP, NFS, Pq, LDL-C, HDL-C, Triglycerides, Lp(a), Lp-PLA2 as well as fasting glucose, HbA1C and microalbuminuria

Radiation:
• Brain and aorta RMI
A magnetic resonance imaging exam will be performed at the Neuroimaging Research Center of the Pitié-Salpêtrière Hospital. This exam will be optimized to fit in 30 minutes. Indeed brain 3D T1 and T2 FLAIR imaging lasts 15 minutes while cine and velocity encoded imaging of the aorta lasts 15 minutes.

Other:
• Adaptative optics
The retina adaptative optic imaging will be performed at the "Unité de prevention des maladies cardiovasculaires" Pitié Salpetrière Hospital. This exam lasts 10 minutes including patient positioning and imaging.

Locations

Country	Name	City	State
France	Unité de prévention des maladies cardiovasculaires Pôle Cardiologie/Métabolisme Hôpital Pitié-Salpétriêre, APHP, 83 bd de l'hôpital,	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Institute of Cardiometabolism and Nutrition, France	France: Fondation de Recherche sur l'Hypertension Artérielle

Country where clinical trial is conducted

France, 

References & Publications (14)

Bollache E, Kachenoura N, Redheuil A, Frouin F, Mousseaux E, Recho P, Lucor D. Descending aorta subject-specific one-dimensional model validated against in vivo data. J Biomech. 2014 Jan 22;47(2):424-31. doi: 10.1016/j.jbiomech.2013.11.009. Epub 2013 Nov 15. — View Citation

Dogui A, Kachenoura N, Frouin F, Lefort M, De Cesare A, Mousseaux E, Herment A. Consistency of aortic distensibility and pulse wave velocity estimates with respect to the Bramwell-Hill theoretical model: a cardiovascular magnetic resonance study. J Cardiovasc Magn Reson. 2011 Jan 27;13:11. doi: 10.1186/1532-429X-13-11. — View Citation

Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, Hall K, Hasegawa K, Hendrie H, Huang Y, Jorm A, Mathers C, Menezes PR, Rimmer E, Scazufca M; Alzheimer's Disease International. Global prevalence of dementia: a Delphi consensus study. Lancet. 2005 Dec 17;366(9503):2112-7. — View Citation

Hanon O, Haulon S, Lenoir H, Seux ML, Rigaud AS, Safar M, Girerd X, Forette F. Relationship between arterial stiffness and cognitive function in elderly subjects with complaints of memory loss. Stroke. 2005 Oct;36(10):2193-7. Epub 2005 Sep 8. — View Citation

Hardy JA, Mann DM, Wester P, Winblad B. An integrative hypothesis concerning the pathogenesis and progression of Alzheimer's disease. Neurobiol Aging. 1986 Nov-Dec;7(6):489-502. Review. — View Citation

Herment A, Kachenoura N, Lefort M, Bensalah M, Dogui A, Frouin F, Mousseaux E, De Cesare A. Automated segmentation of the aorta from phase contrast MR images: validation against expert tracing in healthy volunteers and in patients with a dilated aorta. J Magn Reson Imaging. 2010 Apr;31(4):881-8. doi: 10.1002/jmri.22124. — View Citation

Launer LJ, Ross GW, Petrovitch H, Masaki K, Foley D, White LR, Havlik RJ. Midlife blood pressure and dementia: the Honolulu-Asia aging study. Neurobiol Aging. 2000 Jan-Feb;21(1):49-55. — View Citation

Luchsinger JA, Reitz C, Honig LS, Tang MX, Shea S, Mayeux R. Aggregation of vascular risk factors and risk of incident Alzheimer disease. Neurology. 2005 Aug 23;65(4):545-51. — View Citation

Perlmutter LS, Barrón E, Saperia D, Chui HC. Association between vascular basement membrane components and the lesions of Alzheimer's disease. J Neurosci Res. 1991 Dec;30(4):673-81. — View Citation

Qiu C, Winblad B, Fratiglioni L. The age-dependent relation of blood pressure to cognitive function and dementia. Lancet Neurol. 2005 Aug;4(8):487-99. Review. — View Citation

Redheuil A, Yu WC, Mousseaux E, Harouni AA, Kachenoura N, Wu CO, Bluemke D, Lima JA. Age-related changes in aortic arch geometry: relationship with proximal aortic function and left ventricular mass and remodeling. J Am Coll Cardiol. 2011 Sep 13;58(12):1262-70. doi: 10.1016/j.jacc.2011.06.012. — View Citation

Redheuil A, Yu WC, Wu CO, Mousseaux E, de Cesare A, Yan R, Kachenoura N, Bluemke D, Lima JA. Reduced ascending aortic strain and distensibility: earliest manifestations of vascular aging in humans. Hypertension. 2010 Feb;55(2):319-26. doi: 10.1161/HYPERTENSIONAHA.109.141275. Epub 2010 Jan 11. — View Citation

Rosenbaum D, Koch E, Girerd X, Rossant F, Pâques M. [Imaging of retinal arteries with adaptative optics, feasibility and reproducibility]. Ann Cardiol Angeiol (Paris). 2013 Jun;62(3):184-8. doi: 10.1016/j.ancard.2013.04.017. Epub 2013 May 29. French. — View Citation

Vagnucci AH Jr, Li WW. Alzheimer's disease and angiogenesis. Lancet. 2003 Feb 15;361(9357):605-8. Review. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relationships between retina micro-vascular remodeling and cognitive function in hypertensive patients.		September 2017	No
Secondary	• Associations between cognitive function and proximal aortic stiffness indices estimated from MRI images.		September 2017	No
Secondary	• Associations between retina arteriolar remodelling and cerebrovascular lesions (infarcts, lacuna, and white matter lesions) quantified from MRI images.		September 2017	No
Secondary	• Associations between retina arteriolar remodelling and neurodegenerative lesions (hippocampus atrophy) quantified from MRI images.		September 2017	No
Secondary	• Associations between proximal aortic stiffness and cerebrovascular lesions (infarcts, lacuna, and white matter lesions) quantified from MRI images.		September 2017	No
Secondary	• Associations between proximal aortic stiffness and neurodegenerative lesions (hippocampus atrophy) quantified from MRI images.		September 2017	No
Secondary	• Associations between retina arteriolar remodelling and proximal aortic stiffness indices.		September 2017	No