Pre-FRONTal Brain STability, Key for Action Against Disability in AGing

Cognitive Impairment Clinical Trial

— FRONT STAGE  

Official title:

Pre-FRONTal Brain STability, Key for Action Against Disability in AGing: The FRONT STAGE Project

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04115215
• Other study ID #: FRONT STAGE (PI19/00734)
• Status: Enrolling by invitation
• Phase: N/A
• Start date: March 23, 2020
• Est. completion date: March 23, 2023

Study information

• Verified date: June 2021
• Source: Parc Sanitari Pere Virgili
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Cognitive and mobility impairments are critical contributors to dementia and disability in older adults, and can be caused by neurodegenerative and neurovascular changes at the pre-frontal (PF) brain areas. In a previous technological project funded by ISCiii, the investigators adapted a non-invasive, point-of-care optical methods (fNRIS/fDCS technology) to study PF metabolism and blood flow activation during cognitive and motor tasks, in older adults with and without cognitive impairment. These methods are sensitive to change after physical exercise (PE) and after selectively and safely stimulating PF areas with electrical transcranial direct current stimulation (tCS). PE and tCS have shown benefits for cognition and mobility in the elderly, but their prolonged effect on PF hemodynamic activation has not been studied. Understanding the specific action of these interventions on the brain, and their clinical cognitive and motor impact, is key to fine-tune appropriate treatment strategies. The FRONT STAGE project aims to compare, through a 3 arms single-blind randomized clinical trial, the impact of a 10 weeks, 1 hour/week program of PE (arm 1) Vs PE+tCS (arm 2) and Vs a control group (arm 3, healthy aging sessions and control of cardiovascular risk factors). The PE program is already implemented in primary care, as part of another previous project of the investigators' research group. Outcomes will include the optical measurement of PF metabolism and blood flow and clinical measures of cognitive and physical function. Front STAGE project will recruit 93 older adults with cognitive impairment and slow gait, but without dementia or disability in the activities of daily living (N=31 per arm). They will receive a comprehensive geriatric assessment at baseline, together with the optical, cognitive and physical measures, and will be follow-up at 3 and 6 months. Weekly physical activity through accelerometry will be controlled in analyses. FRONT STAGE project centered on aging and the prevention of dementia and disability, will provide, translationally, more evidence to support and enlarge the clinical application of these interventions, and will contribute to foster further research in this field.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 93
• Est. completion date: March 23, 2023
• Est. primary completion date: March 23, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

Inclusion Criteria:

1. older adults (65 years or older)

2. with Motoric Cognitive Risk Syndrome

3. characterized by impaired cognition (which in our case will be confirmed with a Spanish version of the Montreal cognitive Assessment (MOCA), score between 26 and 21)

4. mobility impairment (measured as slow gait speed<0.8 m/s)

5. without diagnosed clinical neurological or psychiatric diseases

6. with a preserved functional status for the activities of daily living

7. who can walk without help from third parties

Exclusion Criteria:

1. a diagnosis of dementia

2. advanced/terminal disease (life expectancy<1 year)

3. contraindications to exercise and tCS

4. unwilling to give informed consent

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Cognitive Impairment
• Motoric Cognitive Risk Syndrome

Intervention

Behavioral:
• Physical exercise (PE)
This arm includes 10 sessions of multi-component exercise sessions (including aerobic, resistance, flexibility, dual-tasking) of 1 hour/week of functional group exercise, directed to foster empowerment for subsequent continuation of exercise in community-dwelling older adults referred by primary care to a geriatrician and an expert physical therapist. Participants will receive a leaflet with instructions to perform five strength-based exercises and instructors will recommend participants to perform the exercises and walk at least 15 minutes daily.

Device:
• Transcranial current stimulation (tCS)
This arm includes 1 application/week for 10 weeks during PE, through an adapted commercial helmet. Transcranial current stimulation (tCS) is a neural stimulation technique based on electrical stimulation of selected parts of the brain with direct or alternated electrical current (tDCS or tACS) of very low intensity of 1,5 milliamps (mA), using one or more electrodes placed on the skull. tCS is non-invasive (no surgical procedures) and it is painless, as applied in the proposed protocols.

Other:
• Control
Participants of similar profile, randomized to the control group, will undergo weekly 30 minutes educational sessions on healthy aging, including relevant aspects of nutrition, self-care, physical activity, plus measurement of blood pressure, heart rate and peripheral oxygen Hb saturation. These participants will be offered to join the PE program after the 6-months follow-up (end of the study).

Locations

Country	Name	City	State
Spain	Hospital Universitario La Ribera	Alzira	Valencia
Spain	Fundació Ictus	Barcelona
Spain	Institut Català de la Salut	Barcelona
Spain	Parc Sanitari Pere Virgili	Barcelona
Spain	The Institute of Photonic Sciences (ICFO)	Castelldefels	Barcelona

Sponsors (6)

Lead Sponsor	Collaborator
Parc Sanitari Pere Virgili	Fundacio Ictus Malaltia Vascular, Hospital de la Ribera, Institut Català de la Salut, Institute for Photonic Sciences - ICFO, Vall d'Hebron Research Institute (sponsor)

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Spatial temporal parameters of gait	Step length, width and cadence; using the portable 4 meters Protokinetics Zeno computerized carpet.	Baseline (prior to intervention), 3 and 6 months after completion of the intervention.
Other	Total time of daily physical activity	ActivPal devices will be applied for 7 consecutive days to monitor physical activity outside and between exercise sessions, and also in the control group, in order to subsequently adjust the analyses for the activity performed out of the exercise sessions.	7 consecutive days (arms 2 & 3) just after the start of the intervention.
Other	Clinical comorbidity	The Charlson Comorbidity Index is a method of categorizing comorbidities of patients based on the International Classification of Diseases (ICD) diagnosis codes found in administrative data, such as hospital abstracts data. Each comorbidity category has an associated weight (from 1 to 6), based on the adjusted risk of mortality or resource use, and the sum of all the weights results in a single comorbidity score for a patient. A score of zero indicates that no comorbidities were found. The higher the score, the more likely the predicted outcome will result in mortality or higher resource use.	Baseline.
Other	Nutritional status	The Mini Nutritional Assessment Short Form (MNA®-SF) is an effective tool to help identify patients who are malnourished or at risk of malnutrition. Scores range from: 12-14 points, Normal nutritional status; 8-11 points At risk of malnutrition; 0-7 points Malnourished.	Baseline.
Other	Demographics	Age, gender, education, former profession, marital status, living situation and physical barriers, presence of a valid caregiver.	Baseline.
Other	Self-reported quality of life	EuroQol-5D is a standardized instrument for measuring generic health status. It has been widely used in population health surveys, clinical studies, economic evaluation and in routine outcome measurement in the delivery of operational healthcare. This instrument is designed for self-completion and as such captures information directly from the respondent, thereby generating data that conforms with the general requirement of all Patient Reported Outcome (PRO) measures. Total score will be used, with higher scores revealing higher quality of life.	Baseline
Other	Body Mass Index	Weight & Height will be collected and computed to obtain Body Mass Index.	Baseline
Other	Depressive symptoms	The Yesavage GDS-15 items assesses depressive symptoms. The scale consists of 15 yes/no questions. Each question is scored as either 0 or 1 points. The following general cutoff may be used to qualify the severity of depressive symptoms: normal 0-4, >=5 possible depression.	Baseline
Other	Quality of sleep	Total score of the Jenkins questionnaire will be used to estimate quality of sleep. This questionnaire consists of 4 items rated on a 6-point scale. The 4 items ask how frequently during the previous 4 weeks the respondent experienced difficulty falling asleep, difficulty staying asleep, waking up several times per night, and waking up feeling tired and worn out after the usual amount of sleep. A dichotomous index is computed and coded as 1 if the respondents reported that any of the above sleep disturbances occurred 15 or more nights during the previous 4 weeks or as 0, if not. The selection of 15 nights as the cut-off point for sleep disturbance was based on criteria from the DSM-IV-TR, which stipulate that difficulty maintaining/initiating sleep or non-restorative sleep should be present for 3 or more nights per week for at least 1 month. A similar cut-off point for sleep disturbance was used in previous studies.	Baseline
Other	Drugs	Total number of drugs prescribed.	Baseline
Other	Hypertension	Diagnosis of hypertension (yes / no) will be collected as a cardiovascular risk factor.	Baseline
Other	Cholesterol	High cholesterol (yes / no) will be collected as a cardiovascular risk factor.	Baseline
Primary	Changes in hemoglobin oxygenation during functional tasks, as measured using fNIRS+fDCS optical techniques.	Our primary outcome will be prefrontal hemoglobin oxygenation during a) cognitive tests, such as phonetic verbal fluency and calculations (2-forward and 3-backward counting), b) normal gait, c) dual task (walking while counting).; All the measures will be controlled for extra-cerebral and systemic contributions due to variations in heart-rate, oxygen saturation, respiration rate and end-tidal carbondioxide. Various measures such as those derived from accelerometers to account for potential motion artifacts will be also utilized, followed by a multi-subject analysis.	Baseline (prior to intervention), 3 and 6 months after completion of the intervention.
Secondary	Cognitive executive function tests - Phonetic Verbal Fluency	Phonetic verbal fluency will be measured by scoring total number of words (not repeated) per unit of time, with higher rates revealing better performance.	Baseline (prior to intervention), 3 and 6 months after completion of the intervention.
Secondary	Rey Auditory Verbal Learning Test (RAVLT)	Rey Auditory Verbal Learning Test (RAVLT) is a validated neuropsychological test used to assess verbal memory function.	Baseline (prior to intervention), 3 and 6 months after completion of the intervention.
Secondary	Cognitive executive function tests - SDMT	The symbol-digit modalities test (SDMT) is a symbol substitution neuropsychological test that examines a person's attention and speed of processing. Higher scores will indicate better performance.	Baseline (prior to intervention), 3 and 6 months after completion of the intervention.
Secondary	Physical function	The short physical performance battery (SPPB) is a group of measures that combines the results of the gait speed, chair stand and balance tests. It has been used as a predictive tool for possible disability and can aid in the monitoring of function in older people. The scores range from 0 (worst performance) to 12 (best performance), aggregated from the different subtests.	Baseline (prior to intervention), 3 and 6 months after completion of the intervention.
Secondary	Motor function	"Dual task" measure: cost of gait speed reduction when a cognitive task (verbal fluency) is associated during gait, compared to gait alone.	Baseline (prior to intervention), 3 and 6 months after completion of the intervention.
Secondary	Cognitive executive function tests - Digit span	The digit span is a widely used neuropsychological test to assess attention and working memory.	Baseline (prior to intervention), 3 and 6 months after completion of the intervention.
Secondary	Cognitive executive function tests - Trail Making Test	Trail Making Test (TMT A and B) will be perform to assess executive function (attention).	Baseline (prior to intervention), 3 and 6 months after completion of the intervention.