Successful Aging and Frailty

NCT03963050 | Unknown DMC

• 1 other identifier: 27111
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Frailty Syndrome; Cognitive Impairment; Sarcopenia

Keywords

Frailty phenotype; Cognitive Impairment; Sarcopenia; Exercise

Outcome Measures

Primary Outcomes (6)

• 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.

  3 years

• Structural cerebral cortex adaptations (TMS)

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

  3 years

• 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).

  3 years

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

  To assess non-invasively cerebral blood flow (CBF)

  3 years

• Muscle mass alterations (DXA)

  Muscle mass will be assessed with DXA

  3 years

• Alveolar profiles

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

  3 years

Secondary Outcomes (4)

• Changes in muscular fiber type

  3 years

• Changes in neuromuscular control 1

  3 years

• Changes in neuromuscular control 2

  3 years

• Mitochondrial Respiration

  3 years

Study Arms (2)

CF

EXPERIMENTAL

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.

Other: Exercise Training; Other: Exercise Training + Cognitive Training; Other: Control

PF

EXPERIMENTAL

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.

Other: Exercise Training; Other: Exercise Training + Cognitive Training; Other: Control

Interventions

Exercise Training OTHER

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

CF; PF

Exercise Training + Cognitive Training 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.

CF; PF

Control OTHER

NO changes in lifestyle

CF; PF

Eligibility Criteria

• Age: 80 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Universita di Verona: lead

Study Sites (1)

University of Verona

Verona, 37131, Italy

RECRUITING

Related Publications (12)

• 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.

  PMID: 25333486 RESULT

• 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.

  PMID: 24577456 RESULT

• 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.

  PMID: 11328886 RESULT

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

  PMID: 22908189 RESULT

• 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.

  PMID: 28078981 RESULT

• 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.

  PMID: 24381719 RESULT

• 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.

  PMID: 30116492 RESULT

• 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.

  PMID: 29728093 RESULT

• 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.

  PMID: 24715426 RESULT

• 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.

  PMID: 9727941 RESULT

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

  PMID: 1734182 RESULT

• 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.

  PMID: 17030755 RESULT

MeSH Terms

Conditions

Frailty; Cognitive Dysfunction; Sarcopenia; Motor Activity

Interventions

Exercise; Cognitive Training

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Signs and Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Neurological Rehabilitation; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services

Study Officials

• Massimo Venturelli, Ph.D.

  Università degli studi di Verona

  PRINCIPAL INVESTIGATOR

• Maria Romanelli, Ph.D.

  Università degli studi di Verona

  PRINCIPAL INVESTIGATOR

• Federico Schena, Ph.D.

  Università degli studi di Verona

  STUDY DIRECTOR

• Lidia Del Piccolo, Ph.D.

  Università degli studi di Verona

  STUDY DIRECTOR

Central Study Contacts

Manuela Calderara

CONTACT

+39 0458124287; manuela.calderara@univr.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Fellow

Study Record Dates

• First Submitted: May 17, 2019
• First Posted: May 24, 2019
• Study Start: September 1, 2019
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2023
• Last Updated: November 4, 2020

Record last verified: 2020-11

Locations

IT (1)