Successful Aging and Frailty

NCT ID: NCT03963050

Last Updated: 2020-11-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

180 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-09-01

Study Completion Date

2023-12-31

Brief Summary

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Frailty is the term commonly utilized to describe the geriatric syndrome that exposes the elderly to increased risk of negative health-related events. The frailty phenotypes (PF: physical or CF: cognitive) have demonstrated to predict the major negative health-related outcomes in the old population and show extensive similarities with sarcopenia (for PF) or dementia (for CF). However, the role of neurophysiological and biological factors contributing to the physical and cognitive frail condition, and in particular in which way mitochondrial dysfunction, as well as the hypertrophic and atrophic pathways assessed by genes expression, metabolomics and microbiota composition are contributing to these frail conditions, are still under debate. Therefore, the aim of this trial will be to make evidence based on the behaviors and the strategies that promote healthy lifestyle and successful human aging.

Detailed Description

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In the majority of the world, the population is living to a greater age. However, older age is usually associated with elevated risk of several pathologies, as well as age-related organ dysfunctions, which in turn can accelerate functional impairments, disability, or death. To identify this geriatric syndrome the term frailty phenotype has been commonly utilized. In particular, the frailty phenotype can be distinguished in physical frailty (PF) phenotype or cognitive frailty (CF) phenotype.

Despite several groups of researchers tried to develop preventive interventions to counteract the physical and cognitive frail condition of elderly, the success of this task has been tempered by the lack of standardized, and universally agreed protocols. Moreover, the limited knowledge of the neurophysiological, and biological determinants of these conditions has precluded important advances in the research of this domain.

Many factors combine to achieve a successful aging: genetics, health care and healty lifestile. Therefore, the aim of the current trial will be to understand the behaviors and the strategies that promote healthy lifestyle and successful human aging.

Oldest old participants with CF and PF will be selected from the neurorehabilitation unit of the University Hospital of Verona (Italy). Healthy oldest old and young participants will be recruited from the section of Movement Sciences of the University of Verona.

After a first phase of neurophysiological and biological examinations that will involve all the 4 groups, only CF and PF participants will be randomly assigned to an intervention program (physical exercise, physical+cognitive exercise or control). Frail participants assigned to exercise groups will then perform 1 year of intervention, 3 days per week, 1 hour per day. Afterwards, the three groups of intervention will undergo the same neurophysiological and biological examinations of the beginning of the study.

Conditions

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Frailty Syndrome Cognitive Impairment Sarcopenia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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CF

30 participants (randomized in 3 groups) with CF will perform a program of intervention for 1 hour a day, 3 days per week, for 1 year.

Group Type EXPERIMENTAL

Exercise Training

Intervention Type OTHER

The ET program will consist of endurance exercises at 70% of maximal Heart Rate and resistance exercises at 85% of 1 repetition maximum.

Exercise Training + Cognitive Training

Intervention Type OTHER

ET: The intervention program will consist of endurance exercises at 70% of maximal Heart Rate and resistance exercises at 85% of 1 repetition maximum.

CT: The intervention program will be configured as a cognitive rehabilitation and mainly memory rehabilitation: the participants will be trained in practicing restorative and compensatory mnemonic techniques, such as visual imagery, face-name association, calendar, notes and prompts.

Control

Intervention Type OTHER

NO changes in lifestyle

PF

30 participants (randomized in 3 groups) with PF will perform a program of intervention for 1 hour a day, 3 days per week, for 1 year.

Group Type EXPERIMENTAL

Exercise Training

Intervention Type OTHER

The ET program will consist of endurance exercises at 70% of maximal Heart Rate and resistance exercises at 85% of 1 repetition maximum.

Exercise Training + Cognitive Training

Intervention Type OTHER

ET: The intervention program will consist of endurance exercises at 70% of maximal Heart Rate and resistance exercises at 85% of 1 repetition maximum.

CT: The intervention program will be configured as a cognitive rehabilitation and mainly memory rehabilitation: the participants will be trained in practicing restorative and compensatory mnemonic techniques, such as visual imagery, face-name association, calendar, notes and prompts.

Control

Intervention Type OTHER

NO changes in lifestyle

Interventions

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Exercise Training

The ET program will consist of endurance exercises at 70% of maximal Heart Rate and resistance exercises at 85% of 1 repetition maximum.

Intervention Type OTHER

Exercise Training + Cognitive Training

ET: The intervention program will consist of endurance exercises at 70% of maximal Heart Rate and resistance exercises at 85% of 1 repetition maximum.

CT: The intervention program will be configured as a cognitive rehabilitation and mainly memory rehabilitation: the participants will be trained in practicing restorative and compensatory mnemonic techniques, such as visual imagery, face-name association, calendar, notes and prompts.

Intervention Type OTHER

Control

NO changes in lifestyle

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* YH: 30 healthy young (20-25 years old) participants. They must be free of any disease.
* OH: 30 healthy oldest old (80-90 years old) participants. They must be free of any neural or physical disease and any severe chronic disease (CODP, Heart Failure) that can compromise exercise.
* PF: 30 oldest old (80-90 years old) participants. They must be characterized by functional deficits (sarcopenia, osteoporosis and muscle weakness) without cognitive impairment. Additionally, participants cannot be affected by any severe chronic disease that compromise exercise.
* CF: 30 oldest old (80-90 years old) participants. They must be characterized by mild cognitive impairment (MCI) and subjective cognitive decline without functional deficits. Additionally, participants cannot be affected by any severe chronic disease that compromise exercise.

Exclusion Criteria

* Any medication
* Any disease
* General: pregnancy, addictive or previous addictive behavior defined as the abuse of cannabis, opioids or other drugs, carrier of infectious diseases.
* For TMS: Epilepsy, metallic prosthesis, malignant tumor


* Heart failure, angina, pulmonary disease.
* Cognitive frailty (MCI, Alzheimer) or physical frailty (musculoskeletal diseases)
* General: coagulation disorders, pregnancy, addictive or previous addictive behavior defined as the abuse of cannabis, opioids or other drugs, carrier of infectious diseases, suffering from musculoskeletal diseases, suffering from mental illness, inability to cooperate, subjects suffering from known cardiac conditions (e.g., pacemakers, arrhythmias, and cardiac conduction disturbances) or peripheral neuropathy. Moreover, subjects suffering from diabetes, arthritis and under medication will be scored according to specific criteria.
* Assumption of any anticoagulant medication
* Assumption of antiplatelet medications in high dose (es: acetylsalicylic acid \>200mg x day)
* For TMS: Epilepsy, metallic prosthesis, malignant tumor
* For MRI: pacemaker, internal defibrillator or other ferromagnetic implants


* Simultaneous presence of physical frailty and cognitive impairment (CDR=0.5)
* For exercise testing and training: heart failure, angina, pulmonary disease.
* General: coagulation disorders, pregnancy, addictive or previous addictive behavior defined as the abuse of cannabis, opioids or other drugs, carrier of infectious diseases, suffering from musculoskeletal diseases, suffering from mental illness, inability to cooperate, subjects suffering from known cardiac conditions (e.g., pacemakers, arrhythmias, and cardiac conduction disturbances) or peripheral neuropathy. Moreover, subjects suffering from diabetes, arthritis and under medication will be scored according to specific criteria.
* The T-scores for the whole body and PA-projection total spine parameters: According to the World Health Organization (WHO) recommendation, participants will be diagnosed as having osteoporosis when the minimum T-score, measured at any site, will be less than -2.5, osteopenia if T-score between -1 and -2.5 and normal if T-score will be greater than -1 according to the World Health Organization guideline. Diagnosis will be made on basis of lowest T score at any measured site (T score ≥-1 SD = Normal; T score between -1 and -2.5 SD = Low bone mass, and T Score ≤-2.5 SD = Osteoporosis). T-score reference values are provided by the DXA scanner manufacturer.
* Assumption of any anticoagulant medication
* Assumption of antiplatelet medications in high dose (es: acetylsalicylic acid \>200mg x day)
* For TMS: Epilepsy, metallic prosthesis, malignant tumor
* For MRI: pacemaker, internal defibrillator or other ferromagnetic implants
* Decline a priori to participate in the intervention Phase 2 of the study

* Fried's Frailty Phenotype: \< 3 positive characteristics
* Timed-up-and-go test: \<10 sec
* The Multidimensional Prognostic Instrument (MPI): \< 0.66 score
* The GAITRite system: \> 0.9 m/s
* Groningen Frailty Indicator: \<4


* Simultaneous presence of physical frailty and cognitive impairment (CDR=0.5)
* For exercise testing and training: heart failure, angina, pulmonary disease.
* General: coagulation disorders, pregnancy, addictive or previous addictive behavior defined as the abuse of cannabis, opioids or other drugs, carrier of infectious diseases, suffering from musculoskeletal diseases, suffering from mental illness, inability to cooperate, subjects suffering from known cardiac conditions (e.g., pacemakers, arrhythmias, and cardiac conduction disturbances) or peripheral neuropathy. Moreover, subjects suffering from diabetes, arthritis and under medication will be scored according to specific criteria.
* The T-scores for the whole body and PA-projection total spine parameters: According to the World Health Organization (WHO) recommendation, participants will be diagnosed as having osteoporosis when the minimum T-score, measured at any site, will be less than -2.5, osteopenia if T-score between -1 and -2.5 and normal if T-score will be greater than -1 according to the World Health Organization guideline. Diagnosis will be made on basis of lowest T score at any measured site (T score ≥-1 SD = Normal; T score between -1 and -2.5 SD = Low bone mass, and T Score ≤-2.5 SD = Osteoporosis). T-score reference values are provided by the DXA scanner manufacturer.
* Assumption of any anticoagulant medication
* Assumption of antiplatelet medications in high dose (es: acetylsalicylic acid \>200mg x day)
* For TMS: Epilepsy, metallic prosthesis, malignant tumor
* For MRI: pacemaker, internal defibrillator or other ferromagnetic implants
* Decline a priori to participate in the intervention Phase 2 of the study

* Mini Mental State (MMSE): cut-off 23.8
* FCSRT: IFR (immediate free recall) cut off \<19.59; ITR (immediate total recall) cut off\<35; DFR (delayed free recall) cut off \<6.31; DTR (delayed total recall) cut off\<11; index of sensitivity of cueing cut off\<0.9; Number of intrusions cut off\>0
* Digit Span: cut off 3.75
* Digit Span Reversal (WAIS): cut off 2.65
* Rey-Osterrieth Complex Figure Test: cut off copy 28.88 - cut off
* deferred reproduction 9.47
* Trial Making Test A(ENB2): cut off \>93 sec; TMT B (ENB2): cut off \>282 sec; TMT B-A (ENB2): cut off\>186 sec
* Frontal Assessment Battery (FAB): cut off \<13.4
* Phonemic Fluency (ENB2): cut off 3
* Clock Test: cut off \<6.25
* Time up and Go TUG-COG: cut off \>15sec
* Cognitive Function Instrument (partly for the caregiver): no cut-off
* Neuropsychiatric Inventory (for the caregiver): cut-off \>0
* Geriatric Depression Scale: cut-off\>10
Minimum Eligible Age

80 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Universita di Verona

OTHER

Sponsor Role lead

Responsible Party

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Massimo Venturelli, PhD

Research Fellow

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Massimo Venturelli, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Università degli studi di Verona

Maria Romanelli, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Università degli studi di Verona

Federico Schena, Ph.D.

Role: STUDY_DIRECTOR

Università degli studi di Verona

Lidia Del Piccolo, Ph.D.

Role: STUDY_DIRECTOR

Università degli studi di Verona

Locations

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University of Verona

Verona, , Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Manuela Calderara

Role: CONTACT

+39 0458124287 ext. 00393209033512

Facility Contacts

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Manuela Calderara

Role: primary

+390458124287

References

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Hatse S, Brouwers B, Dalmasso B, Laenen A, Kenis C, Schoffski P, Wildiers H. Circulating MicroRNAs as easy-to-measure aging biomarkers in older breast cancer patients: correlation with chronological age but not with fitness/frailty status. PLoS One. 2014 Oct 21;9(10):e110644. doi: 10.1371/journal.pone.0110644. eCollection 2014.

Reference Type RESULT
PMID: 25333486 (View on PubMed)

Tan L, Yu JT, Tan MS, Liu QY, Wang HF, Zhang W, Jiang T, Tan L. Genome-wide serum microRNA expression profiling identifies serum biomarkers for Alzheimer's disease. J Alzheimers Dis. 2014;40(4):1017-27. doi: 10.3233/JAD-132144.

Reference Type RESULT
PMID: 24577456 (View on PubMed)

Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001 May 1;29(9):e45. doi: 10.1093/nar/29.9.e45.

Reference Type RESULT
PMID: 11328886 (View on PubMed)

Mayeux R, Stern Y. Epidemiology of Alzheimer disease. Cold Spring Harb Perspect Med. 2012 Aug 1;2(8):a006239. doi: 10.1101/cshperspect.a006239.

Reference Type RESULT
PMID: 22908189 (View on PubMed)

Pedrinolla A, Schena F, Venturelli M. Resilience to Alzheimer's Disease: The Role of Physical Activity. Curr Alzheimer Res. 2017 Apr 3;14(5):546 - 553. doi: 10.2174/1567205014666170111145817.

Reference Type RESULT
PMID: 28078981 (View on PubMed)

Popa-Wagner A, Mitran S, Sivanesan S, Chang E, Buga AM. ROS and brain diseases: the good, the bad, and the ugly. Oxid Med Cell Longev. 2013;2013:963520. doi: 10.1155/2013/963520. Epub 2013 Dec 5.

Reference Type RESULT
PMID: 24381719 (View on PubMed)

Rusanova I, Diaz-Casado ME, Fernandez-Ortiz M, Aranda-Martinez P, Guerra-Librero A, Garcia-Garcia FJ, Escames G, Manas L, Acuna-Castroviejo D. Analysis of Plasma MicroRNAs as Predictors and Biomarkers of Aging and Frailty in Humans. Oxid Med Cell Longev. 2018 Jul 18;2018:7671850. doi: 10.1155/2018/7671850. eCollection 2018.

Reference Type RESULT
PMID: 30116492 (View on PubMed)

Princivalle A, Monasta L, Butturini G, Bassi C, Perbellini L. Pancreatic ductal adenocarcinoma can be detected by analysis of volatile organic compounds (VOCs) in alveolar air. BMC Cancer. 2018 May 4;18(1):529. doi: 10.1186/s12885-018-4452-0.

Reference Type RESULT
PMID: 29728093 (View on PubMed)

Alsop DC, Detre JA, Golay X, Gunther M, Hendrikse J, Hernandez-Garcia L, Lu H, MacIntosh BJ, Parkes LM, Smits M, van Osch MJ, Wang DJ, Wong EC, Zaharchuk G. Recommended implementation of arterial spin-labeled perfusion MRI for clinical applications: A consensus of the ISMRM perfusion study group and the European consortium for ASL in dementia. Magn Reson Med. 2015 Jan;73(1):102-16. doi: 10.1002/mrm.25197. Epub 2014 Apr 8.

Reference Type RESULT
PMID: 24715426 (View on PubMed)

Buxton RB, Frank LR, Wong EC, Siewert B, Warach S, Edelman RR. A general kinetic model for quantitative perfusion imaging with arterial spin labeling. Magn Reson Med. 1998 Sep;40(3):383-96. doi: 10.1002/mrm.1910400308.

Reference Type RESULT
PMID: 9727941 (View on PubMed)

Detre JA, Leigh JS, Williams DS, Koretsky AP. Perfusion imaging. Magn Reson Med. 1992 Jan;23(1):37-45. doi: 10.1002/mrm.1910230106.

Reference Type RESULT
PMID: 1734182 (View on PubMed)

Du AT, Jahng GH, Hayasaka S, Kramer JH, Rosen HJ, Gorno-Tempini ML, Rankin KP, Miller BL, Weiner MW, Schuff N. Hypoperfusion in frontotemporal dementia and Alzheimer disease by arterial spin labeling MRI. Neurology. 2006 Oct 10;67(7):1215-20. doi: 10.1212/01.wnl.0000238163.71349.78.

Reference Type RESULT
PMID: 17030755 (View on PubMed)

Other Identifiers

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27111

Identifier Type: -

Identifier Source: org_study_id