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Role of Hypoxia Ans Sleep Fragmentation in Alzheimer's Disease. and Sleep Fragmentation.

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ClinicalTrials.gov Identifier: NCT02814045
Recruitment Status : Completed
First Posted : June 27, 2016
Last Update Posted : March 22, 2021
Sponsor:
Information provided by (Responsible Party):
Ferran Barbe, Sociedad Española de Neumología y Cirugía Torácica

Brief Summary:

Alzheimer's Disease (AD) is the most prevalent neurodegenerative disease, manifested as an initial deficit of episodic memory that evolves into a global cognitive and psychosocial dysfunction and which prevalence is increasing around the world. Sleep disturbance is frequent since early stages of the disease and sleep fragmentation had been demonstrated increase the production of amyloid peptide (AB) (main pathological hallmark) in non-demented population. Obstructive Sleep Apnea (OSA), which consist in intermittent hypoxia and sleep fragmentation, is a major health problem with multiple systemic effects and it's very prevalent in AD. However, the influence of this comorbidity on the cognitive evolution of AD patients remains unknown. The investigation of neurobiological markers and sleep recording may reveal potential mechanisms of neurodegeneration and explain the influence of sleep fragmentation and/or hypoxia on cognitive decline.

To fill those gaps, investigators will perform a multidisciplinary and translational project to assess the progression of symptoms in AD patients, diagnosis of sleep disturbance and new biomarkers of progression of the disease.

The present proposal is going to be developed by coordination of different expertises that will be range from the clinical research conducted by a medical neurologist, to the animal model and most molecular work, to be done by an experimented group in mouse work.


Condition or disease
Alzheimer's Disease Obstructive Sleep Apnea

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Study Type : Observational
Actual Enrollment : 144 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Impact of Obstructive Sleep Apnea in the Evolution of Alzheimer Disease. Role of Hypoxia and Sleep Fragmentation
Actual Study Start Date : November 2015
Actual Primary Completion Date : June 2017
Actual Study Completion Date : July 2017


Group/Cohort
Alzheimer with OSA
Alzheimer with OSA after PSG
Alzheimer without OSA
Alzheimer without OSA after PSG



Primary Outcome Measures :
  1. Change from baseline in cognitive scores on the Disease Assessment Scale-cognitive at 12 months in patients with mild AD with and without OSA. [ Time Frame: One year ]
    For this objective we will recruit consecutively 72 patients with OSA and another 72 patients without OSA from the same population of patients with mild initial AD. We will use extensive neuropsychological battery at baseline and at 12 month and polysomnography (PSG) to select both groups of patients at baseline.


Secondary Outcome Measures :
  1. Differential pattern of biomarkers at baseline in in patients with mild AD with and without OSA. [ Time Frame: One year ]
    For this objective we will use CSF (ELISA will be employed to detect the levels of hypoxia-inducible factor 1-alpha (HIF-1alpha), vascular endothelial growth factor (VEGF), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF); and CSF biomarkers of AD as AB42, tau and phosphotau. Lipidaemic and metabolomic analyses will be performed on both, blood sample and CSF. Brain MRI (hippocampal volume, specific patterns of cerebral perfusion and spectroscopy) and actigraph registry. Blood samples to determine inflammatory markers (TNF-alpha, Interleukine-6 and Interleukine-8), the Thiobarbituric Acid Reactive Substances (TBARS) and genotyping APOE4 will be preformed. We will analyze the correlation of these biological biomarkers with cognitive and behavioural progression in OSA and non-OSA AD patients.


Biospecimen Retention:   Samples With DNA
APoE4


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Ages Eligible for Study:   50 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
We prospectively will studied consecutive patients with new diagnosis of mild probable Alzheimer's Disease by a neurologist. We will define Alzheimer's Disease according NIA-AA criteria.
Criteria

Inclusion Criteria:

  1. Patients diagnosed of mild probable AD according to NIA-AA criteria (MMSE>20).
  2. Informed Consent Form signed by the patient (and/or if applicable the legal representative if different from the responsible caregiver) and the responsible caregiver.
  3. The patient has a knowledgeable and reliable caregiver who will accompany the patient to all clinic visits during the study.
  4. Absence of visual and hearing problems that, in the investigator's judgement, difficult for compliance with the study procedures.

Exclusion Criteria:

  1. Previous diagnosis of OSA.
  2. Severe Alzheimer's disease, other types of dementia or patients with mild Alzheimer's disease with current acetylcholinesterase inhibitors or memantine treatment.
  3. Presence of any previously diagnosed sleep disorder: narcolepsy, insomnia, chronic lack of sleep.
  4. Having serious comorbidities: cancer, excessive intake of alcohol (>280 gr/week), severe depression, severe renal or hepatic insufficiency, severe cardiac or respiratory failure.
  5. Currently receiving an investigational drug or device.
  6. Patient or family declining to take part.
  7. Disabling drowsiness not justifiable by any other cause.
  8. The patient has MRI evidence of hydrocephalus, stroke, a space-occupying lesion, cerebral infection or any clinically significant central nervous system disease other than AD.
  9. The patient suffers from mental retardation, organic mental disorders, or mental disorders due to a general medical condition (DSM-IV-TR™ criteria).
  10. The patient has an untreated vitamin B12 or folate deficiency that is considered clinically significant, or has clinical and laboratory evidence of untreated thyroid disease. Patients with vitamin B12 or folate deficiency may be enrolled in the study provided they have been on a supplement therapy for >3 months prior to the Screening Visit and are stable. Patients with thyroid disease may be enrolled in the study provided they are stable and euthyroid.
  11. Patient on betablockers, antidepressants, neuroleptics, hypnotics, or they have been removed 15 days before conducting polysomnography (PSG).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02814045


Locations
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Spain
Hospital santa Maria
Lleida, Catalonia, Spain, 25198
Hospital Santa Maria Lleida
Lleida, Spain, 25198
Sponsors and Collaborators
Sociedad Española de Neumología y Cirugía Torácica
Investigators
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Principal Investigator: Gerard Piñol, Md;PhD Hospital Santa Maria
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Ferran Barbe, PhD, Sociedad Española de Neumología y Cirugía Torácica
ClinicalTrials.gov Identifier: NCT02814045    
Other Study ID Numbers: 464/C/2014
First Posted: June 27, 2016    Key Record Dates
Last Update Posted: March 22, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Ferran Barbe, Sociedad Española de Neumología y Cirugía Torácica:
biomarkers, sleep fragmentation, intermittent hypoxia
Additional relevant MeSH terms:
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Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Alzheimer Disease
Sleep Deprivation
Hypoxia
Apnea
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Neurologic Manifestations