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Autophagy and Pathological Aging (AVP)

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ClinicalTrials.gov Identifier: NCT03175874
Recruitment Status : Recruiting
First Posted : June 5, 2017
Last Update Posted : February 7, 2018
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Nice

Brief Summary:

Autophagy is recognized as a central mechanism for the regulation of aging. . Osteoporosis (OA) and Alzheimer's disease (AD) are two forms of pathological aging, sometimes entangled, including an over-risk of OP in AD and degradation of cognitive functions after OP fracture, but the link between These two pathologies remain poorly understood.

The aim of this prospective pilot study is to evaluate the level of autophagy of osteocytes (OST) in postmenopausal women with OP and to explore the hypothesis that the defect of autophagy is one of the physiopathological links of the OP During the MA


Condition or disease Intervention/treatment Phase
Osteoporosis Procedure: Hip bone sampling Not Applicable

Detailed Description:

Autophagy is a ubiquitous cellular mechanism that degrades and recycles toxic waste from cells. It is recognized as a central mechanism for the regulation of aging. Osteoporosis (OA) and Alzheimer's disease (AD) are two forms of pathological aging, sometimes entangled, including an over-risk of OP in AD and degradation of cognitive functions after OP fracture, but the link between These two pathologies remain poorly understood. In Alzheimer's disease (AD), a deficiency of autophagy is found both clinically and fundamentally. In animal studies, animal studies have shown that autophagy is involved in the differentiation, function and survival of bone cells, decreases with age and that a defect in autophagy is accompanied by a decrease in The bone mass. To date, we do not have human data on the autophagic capacities of bone cells in OP and AD.

The aim of this prospective pilot study is to evaluate the level of autophagy of osteocytes (OST) in postmenopausal women with OP and to investigate the hypothesis that the defect of autophagy is one of the physiopathological links of the OP During the MA.

The main objective is to determine, in two subgroups with or without Alzheimer's disease, whether there is an association between bone status and the level of autophagy of OST in postmenopausal women (OP versus non-OP)

Secondary objectives are to determine whether there is an association between the level of autophagy of the OST and the bone parameters (bone mineral density, serum vitamin D) and to compare in OP women the level of autophagy of the OST Of AM patients vs no MA.

Study population: Postmenopausal women over the age of 65 benefiting from the implantation of a hip prosthesis: 30 with an OP fracture of the femoral neck (15 non-MA and 15 MA, the cognitive status being determined by MMSE And IADL 1 month after the fracture) and 30 controls performed for osteoarthritis, free from OP (antecedents + bone mineral density) and MA (MMSE and IADL).

Primary endpoint: Quantification of autophagy (LC3II and SQSTM1 / p62) by Western blotting of purified OST proteins from a bone sample from resected femoral heads during laying of a total prosthesis Of hip.

Secondary endpoints: Bone mineral density of femoral neck and total hip (T-score and g / cm²) measured by X-ray biphotonic absorptiometry (Hologic QDR 4500) and serum 25 OH vitamin D (ng / ml).

Expected benefits: to better understand the role of autophagy in the pathophysiology of post-menopausal OP and AD in human pathology. Ultimately, it could potentially contribute to the design of new therapeutics targeting autophagy in the management of osteoporosis and more generally pathological aging.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description: Quantification of autophagy (LC3II and SQSTM1 / p62) by Western blotting of purified OST proteins from a bone sample from resected femoral heads during laying of a total hip prosthesis.
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: AVP Study: Autophagy and Pathological Aging Human Study in Osteoporosis With or Without Dementia of Alzheimer's Type
Actual Study Start Date : December 20, 2017
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : February 2020


Arm Intervention/treatment
osteoporosis and alzheimer
patient with osteoporosis and alzheimer hospitalized for total hip prosthesis.
Procedure: Hip bone sampling
Quantification of autophagy (LC3II and SQSTM1 / p62) by Western blotting of purified OST proteins from a bone sample

osteoporosis without alzheimer
Patient with osteoporosis without alzheimer hospitalized for total hip prosthesis.
Procedure: Hip bone sampling
Quantification of autophagy (LC3II and SQSTM1 / p62) by Western blotting of purified OST proteins from a bone sample

Patient with arthrosis without alzheimer
Patient with arthrosis without alzheimer hospitalized for total hip prosthesis.
Procedure: Hip bone sampling
Quantification of autophagy (LC3II and SQSTM1 / p62) by Western blotting of purified OST proteins from a bone sample




Primary Outcome Measures :
  1. Quantification of autophagy [ Time Frame: at inclusion ]
    Quantification of autophagy (LC3II and SQSTM1 / p62) by Western blotting of purified OST proteins from a bone sample from resected femoral heads


Secondary Outcome Measures :
  1. Bone mineral density [ Time Frame: at inclusion ]
    Bone mineral density of femoral neck and total hip (T-score and g / cm²) as measured by X-ray biphotonic absorptiometry (Hologic QDR 4500)

  2. 25 OH vitamin D (ng/ml). [ Time Frame: at inclusion ]
    25 OH vitamin D (ng/ml) in serum



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Ages Eligible for Study:   65 Years and older   (Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Inclusion criteria for both groups:

  • Women > 65 y: 2 groups

Inclusion criteria for Osteoporosis group (Alzheimer and non-Alzheimer):

  • Osteoporotic femoral neck fracture requiring hip remplacement and fullfilling WHO definition of osteoporosis. Without any cognitive impairment for the first subgroup (MMSE > 26 and normal IADL) and with a final diagnosis of alzheimer disease in the other subgroup (DSM-IV-TR)

Inclusion criteria for Control group:

  • Non osteoporotic (no fragility fracture (clinical or on VFA) and bone mineral density T-score > 2.5 SD at all sites)
  • No cognitive impairment (MMSE > 26 and normal IADL)

Exclusion Criteria:

Non-Inclusion Criteria for both groups:

  • Other pathologies associated with autophagy: Parkinson's disease, Crohn's disease, cancers, myopathies, type 2 diabetes
  • Méd Medications interfering with autophagy: current corticosteroids, parathyroid hormone, estrogen, chloroquine, hydroxychloroquine, lithium, metformin, bisphosphonates,
  • Dementia of non-Alzheimer type

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): NCT03175874


Contacts
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Contact: Veronique BREUIL, PhD 0492035512 breuil.v@chu-nice.fr

Locations
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France
BREUIL Recruiting
Nice, France, 06000
Contact: VERONIQUE BREUIL, MD    4 92 03 55 12 ext +33      
Sponsors and Collaborators
Centre Hospitalier Universitaire de Nice
Investigators
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Principal Investigator: Veronique BREUIL, PhD Centre Hospitalier Universitaire de Nice

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Responsible Party: Centre Hospitalier Universitaire de Nice
ClinicalTrials.gov Identifier: NCT03175874     History of Changes
Other Study ID Numbers: 17-PP-03
First Posted: June 5, 2017    Key Record Dates
Last Update Posted: February 7, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Centre Hospitalier Universitaire de Nice:
Osteoporosis
Alzheimer Disease

Additional relevant MeSH terms:
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Osteoporosis
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Metabolic Diseases