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Frailty SyndromeSAFeNCT03963050

Successful Aging and Frailty

A study testing Exercise Training and Exercise Training + Cognitive Training in people with Frailty Syndrome and Cognitive Impairment, run by Universita di Verona at 1 site in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 80 to 90 yearsHealthy volunteers can take part
Conditions the study is for
Frailty Syndrome, Cognitive Impairment, Sarcopenia
What is being tested?
Exercise Training and Exercise Training + Cognitive Training
Could I receive a placebo?
No, everyone receives an active treatment
How many people
180 participants
Where
1 siteItaly
Study dates
1 Sep 2019to 31 Dec 2023
Phase
Interventional
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 80 to 90 years
  • All sexes
  • Healthy volunteers accepted
  • Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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)
Show all 50Show fewer
  • 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
  • Cut-off exclusion criteria of PF:
  • 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
  • Cut-off exclusion criteria of CF:
  • 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

Trial locations and contacts

1 site in 1 country.

Manuela Calderara contact

+39 0458124287 ext. 00393209033512

manuela.calderara@univr.it

Italy1 site, 1 recruiting

  • University of Verona

    Verona, 37131

    Manuela Calderara, +390458124287, manuela.calderara@univr.it

    Massimo Venturelli, Ph.D.

    Recruiting

Other trials in Italy

About this study

Official title: Molecular and Functional Basis of Successful Aging and Frailty

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.

Read the detailed description

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.

Being tested
Exercise Training, Exercise Training + Cognitive Training, Control
Keywords
Frailty phenotype, Cognitive Impairment, Sarcopenia, Exercise
Medical subject headings
Frailty, Cognitive Dysfunction, Sarcopenia, Motor Activity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Exercise TrainingOther

    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 TrainingOther

    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.

  • ControlOther

    NO changes in lifestyle

Study groups in NCT03963050
Study groupRoleWhat they receive
CFExperimental30 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.
Receives: Other: Exercise Training; Other: Exercise Training + Cognitive Training; Other: Control
PFExperimental30 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.
Receives: Other: Exercise Training; Other: Exercise Training + Cognitive Training; Other: Control

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Expression of potential biomarkers (circulating miRNA)

    Noncoding RNAs, in particular, microRNAs (miRNAs), are a new regulatory system which plays a pivotal role in skeletal muscle adaptation and repairing.

    Measured: 3 years

  2. Structural cerebral cortex adaptations (TMS)

    Single-pulse TMS will be used to map the brain area representing the vastus lateralis (VL).

    Measured: 3 years

  3. Functional cerebral cortex adaptations (TMS)

    Single-pulse TMS will be used to investigate the excitability of the corticospinal system. A double-cone coil will be used to stimulate the leg area of the primary motor cortex (M1).

    Measured: 3 years

  4. Modifications in the metabolism of cerebral areas (ASL-MRI)

    To assess non-invasively cerebral blood flow (CBF)

    Measured: 3 years

  5. Muscle mass alterations (DXA)

    Muscle mass will be assessed with DXA

    Measured: 3 years

  6. Alveolar profiles

    Changes in biogenic volatile organic compound concentrations can be used to mirror metabolic or pathophysiological processes in the whole body

    Measured: 3 years

Secondary outcomes (4)

  1. Changes in muscular fiber type

    Outcome of the changes in fiber typing on the components of the muscle mechanics in each group and Pre-Post intervention in CF and PF groups will be evaluated.

    Measured: 3 years

  2. Changes in neuromuscular control 1

    The force rate of development during a maximum voluntary contraction and a tetanic stimulation will be compared in order to estimate the role of central command flow to the muscle in changing the efficiency of the tension development at the tendon.

    Measured: 3 years

  3. Changes in neuromuscular control 2

    The EMG envelope rate of development during a maximum voluntary contraction and a tetanic stimulation will be compared in order to estimate the role of central command flow to the muscle in changing the efficiency of the tension development at the tendon.

    Measured: 3 years

  4. Mitochondrial Respiration

    Changes in mitochondrial respiration function will be measured to asses the level of mitochondrial dysfunction.

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 May 2019
  2. Study start1 Sep 2019
  3. Primary completion31 Dec 2022 (estimated)
  4. Study completion31 Dec 2023 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
180 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03963050
Sponsor's protocol ID
27111
Acronym
SAFe
Status last verified
Nov 2020
First submitted
17 May 2019
Last updated
4 Nov 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 25333486

  • 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.

    PubMed 24577456

  • 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.

    PubMed 11328886

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

    PubMed 22908189

  • 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.

    PubMed 28078981

  • 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.

    PubMed 24381719

  • 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.

    PubMed 30116492

  • 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.

    PubMed 29728093

  • 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.

    PubMed 24715426

  • 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.

    PubMed 9727941

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

    PubMed 1734182

  • 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.

    PubMed 17030755

Questions about this trial

What is this clinical trial studying?

A study testing Exercise Training and Exercise Training + Cognitive Training in people with Frailty Syndrome and Cognitive Impairment, run by Universita di Verona at 1 site in Italy.

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 4 inclusion and 50 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: status not confirmed, as of the sponsor's last update on 4 Nov 2020. 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 Italy. 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?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Manuela Calderara (+39 0458124287 ext. 00393209033512, manuela.calderara@univr.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Expression of potential biomarkers (circulating miRNA) (time frame: 3 years). The study lists 6 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 NCT03963050, which also lists 12 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 4 Nov 2020.

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