ItaliaN Study With Tailored Multidomain Interventions to Prevent Functional and Cognitive Decline in Community-dwelling Older Adults

Age-related Cognitive Decline Clinical Trial

— IN TeMPO  

Official title:

ItaliaN Study With Tailored Multidomain Interventions to Prevent Functional and Cognitive Decline in Community-dwelling Older Adults

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06248723
• Other study ID #: IN TeMPO
• Status: Not yet recruiting
• Phase: N/A
• Start date: March 2024
• Est. completion date: March 2026

Study information

• Verified date: February 2024
• Source: University of Milano Bicocca
• Contact: Carlo Ferrarese
• Phone: 0392333595
• Email: carlo.ferrarese[@]unimib.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this interventional non-pharmacological study is to investigate the effects of a multi-domain intervention ( "active intervention"), compared to that followed by normal clinical practice ("self-guided intervention"), in older adults. The primary objective is whether these interventions can prevent functional and cognitive decline in at-risk subjects.

The multi-domain interventions will include physical exercise, a Mediterranean diet-based nutritional plan, cognitive training, regular medical check-ups, oral hygiene treatments and counseling, monitoring and counseling on visual and auditory abilities, counseling on sleep hygiene and treatment, control of cardiovascular, metabolic, and infectious risk factors, adjustment of drug therapy, suggestions for improving social interactions.

Description:

The study is multicentric and will include 10 centers. Patients will be enrolled either through their General Practitioners (GPs), which will then refer back to their reference centers, or through the centers themselves.

Patients will undergo a screening visit, which will include a multi-faceted evaluation of cognitive function, physical and functional efficiency, and cardiovascular and cognitive decline risk factors. Procedures to be carried out during the screening visit include:

• Collection of socio-demographic data (age, sex, marital status, cohabitation, level of education, social interactions), clinical details (medical and medication history), and evaluation of inclusion/exclusion criteria

• Assessment of the degree of frailty through the Primary Care Frailty Index (PC-FI)

• Assessment of the presence of increased risk of developing dementia through the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score

• Assessment of cognitive performance through the General Practitioner assessment of COGnition (GPCOG)

• Assessment of cognitive performance through the Rey Auditory Verbal Learning Test - immediate

• Assessment of functional status by Short Physical Performance Battery (SPPB) tests

• Nonverbal interference tests

• Assessment of cognitive performance through the Rey Auditory Verbal Learning online version (RAVL-T delayed)

• Collection of self-administered scales for cognitive performance assessment through the Test Your Memory - Italian (TYM-I) scale.

Then, eligible patients will be enrolled for the second, active intervention phase of the study, which will include a baseline visit and 3 follow-up visits, at 6, 12, and 18 months.

During these visits, primary and secondary endpoint outcomes will be collected according to protocol.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 1340
• Est. completion date: March 2026
• Est. primary completion date: March 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 60 Years and older

Eligibility

Inclusion Criteria:

• Aged 60 or older

• Mild/moderate vulnerability (Primary Care Frailty Index score between 0.07 and 0.21)

• Cardiovascular risk factors, Ageing and Incidence of Dementia (CAIDE) > 6

• Clinical Dementia Rating (CDR) = 0.5

• Presence of increased risk of developing dementia by family history (= 1 family member with dementia) and/or at least one modifiable risk factor, with Lifestyle Index =2. Lifestyle index evaluation: each "Yes" answer to the following questions = 1 point.

1. Physical activity less than 2.5 hours per week (defined as physical activity intense enough to lead to sweating and breathlessness)*

2. Diet: less than 5 servings of fruits and vegetables per day*

3. Diet: less than 2 servings of fish per week*

4. Hypertension: diagnosed by a physician or on medication, or Systolic Blood Pressure (SBP)>140 mmHg, or Diastolic Blood Pressure (DBP)>90 mmHg)

5. Diabetes: type 1 or type 2 diagnosed by a physician, or on medication, or HbA1C =7 % in the previous 6 months

6. Sleep disturbances, depressive symptoms, or mental/physical stress symptoms, for at least 1 month, judged by the physician to be disabling in daily life

7. BMI = 25 kg/m^2*

8. Alcohol: > 21 alcohol units/week*. *Based on international and WHO guidelines.

• Informed consent freely given and acquired before the start of the study

Exclusion Criteria:

• Diagnosis of dementia or suspected dementia following the screening visit

• CDR > 0.5

• Residents in residential facilities for the elderly

• Inability to consent to informed consent and/or actively participate in study interventions, according to clinical judgment

• Any condition that prevents safe involvement in the intervention and/or cooperation in the study. For example, a significant neurological or psychiatric condition, including but not limited to brain tumors (benign or malignant), major psychiatric disorders (e.g. current major depressive disorder, schizophrenia, schizoaffective disorder or bipolar disorder), recent brain hemorrhage (parenchymal or subdural), history of concussive head trauma with persistent or significant neurological outcomes, known morpho-structural abnormalities in the brain, active alcohol/drug abuse, active uncontrolled disease of any major organ system; history within the last six months of any acute disease of a major organ system requiring emergency care or hospitalization, including revascularization procedures; severe renal or hepatic insufficiency; unstable or poorly controlled diabetes mellitus, hypertension, or heart failure; malignant neoplasms within the past 3 years (except basal cell carcinoma or squamous cell carcinoma in situ of the skin or localized prostate adenocarcinoma in male participants); any clinically relevant abnormality in blood parameters; severe loss of vision, smar or communication ability, such as to prevent cooperation.

• Enrollment in other trials

• High performance on screening memory tests: RAVL-T immediate score >48 (score ranges 0-75), RAVL-T delayed >10 (score ranges 0-15)

• Planned transfers from the municipality of residence during the duration of the study for a duration longer than 2 weeks.

Related Conditions & MeSH terms

• Age-related Cognitive Decline
• Cognitive Dysfunction

Intervention

Other:
• Nutritional intervention
The objectives of the dietary intervention will be in accordance with the principles of the Mediterranean diet. Weekly menus will be provided that ensure a balanced intake of the various nutrients, according to the objectives outlined in the study protocol, including a reduction in saturated fatty acids (with proportionately more mono- and polyunsaturated fatty acids), promotion of fiber sources and reduction of sugars, adequate protein and micronutrient intake. They will be accompanied by specific dietary patterns that can be individualized based on weight, comorbidities and personal preferences. The need for weight loss or gain will be assessed on an individual basis. Dietary interventions will include group and individual sessions, and will be conducted by dietitians and nutritionists in a harmonized manner among the centers. The first meeting will be in-person and will be held at the subject's clinical center of enrollment. Follow-up will be conducted through online meetings.
• Physical exercise
The physical activity protocol will be geared to the principles of progressive and individualized loading, in group sessions supervised by a physical therapist within gyms for the strength and balance training portion, and in moderate to intense aerobic activities based on individual preferences and characteristics. The physiotherapist will conduct an individual assessment and develop personalized programs for all participants. Exercise sessions will be held 2-3 times a week.
• Cognitive training
Participants will be evaluated through a Cognitive and Psychological Assessment, which will allow measurement of each participant's cognitive functioning and well-being. Computerized cognitive training (CCT) using Brain HeadQuarter (BrainHQ) or similar software will be used as a cognitive intervention. The CCT includes game-based adaptive exercises that target attention, intelligence, memory, navigation, processing speed and social skills. The training will consist of 72 sessions for 24 weeks (about six months), at least three times a week.
• Oral hygiene
Participants will be referred for evaluation at dental hygiene offices. As part of the study, participants will also undergo anticholinergic burden calculation, screening for risk factors for oral diseases (smoking, alcohol), and reduction in the frequency of sugar intake through dietary intervention will be sought. Participants will also undergo the Oral Health Assessment Tool rating scale.
• Sleep quality
During the visits, participants' sleep will be assessed, either by clinical interview or by scales. Participants will also have the opportunity to assess their own sleep via wearable devices. If sleep hygiene issues are detected, advice based on currently available scientific evidence will be provided. If, on the other hand, a suspicion of sleep disorders, including, for example, obstructive sleep apnea syndrome, restless legs syndrome, insomnia, or Rapid Eye Movement (REM) sleep disorder, is raised from the medical history, participants will be referred to the relevant specialists for diagnosis and treatment of such problems.
• Control of cardiovascular, metabolic, and infectious risk factors
Measurements of blood pressure, weight, BMI, abdominal circumference, and advice on health promotion and healthy lifestyle will be provided. Recommendations on adherence to the Piano Nazionale di Prevenzione Vaccinale (PNPV) will also be provided.
• Pharmacological evaluation
Evaluation of prescriptive appropriateness (STOP&START and Beers criteria) and calculation of anticholinergic burden (ACB calculator) will be carried out by a geriatrician, with rationalization of therapy and, where possible, de-prescribing.

Behavioral:
• Socializing
To encourage socialization, proposed activities will be carried out as much as possible in groups of 10-12 people, and outdoor group activities will be suggested on a biweekly basis (e.g., walks in parks). On a monthly basis, the nurse and psychologist will organize motivational and check-up meetings (in recreation centers/via telematics) in order to promote adherence to the protocol, collect questions and stimulate participants. Social activity will also be implemented in the context of all interventions, for example through: Physical activity in groups or pairs, including dance or choir activities where possible Opportunities for further cognitive stimulation in groups through games (e.g., chess, cards, etc.) Proposal to cook, eat or shop together Group sessions with dietitian

Other:
• Self-administered interventions
Subjects in the control group will receive regular health advice in the same domains as the intervention group, via dedicated app and/or access to the dedicated portal on the Age-It website. Such advice and information will be timed to encourage adherence. In addition, participants randomized to the self-guided intervention will receive an initial counseling session of 30-60 minutes on all domains covered by the study, where guidelines for healthy diet, physical and cognitive activity, benefits of social activity, information on cardiovascular risk factors, as well as sleep, oral hygiene will be explained. Subjects will therefore be treated as per normal clinical practice, albeit with the help of dedicated apps and counseling session.

Locations

Country	Name	City	State
Italy	Fondazione IRCCS San Gerardo dei Tintori	Monza

Sponsors (2)

Lead Sponsor	Collaborator
University of Milano Bicocca	European Union

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Modified Neuropsychological Test Battery (mNTB) score	Participants will be scored through the mNTB to assess their cognitive state at baseline and cognitive changes at follow-ups. The mNTB score is a composite score for a battery of 14 tests total. The outcome measure is a z-score, it has no minimum or maximum value. A higher score means a better outcome.	The score will be taken at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6 follow up, Month 12 follow up, and Month 18 follow up. The tests take around 90 minutes overall.
Secondary	Short Physical Performance Battery (SPPB) score	Minimum score: 0, maximum score: 12, a higher score means a better performance.	The score will be taken at Day 0 Screening visit, at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.
Secondary	4-m gait speed test - time	Time needed to walk 4 meters (in seconds). A higher time means a worse performance.	The test will be repeated at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.
Secondary	4-m gait speed test - speed	Walking speed (in meters per second). A higher speed means a better performance.	The test will be repeated at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.
Secondary	Hand grip test	Hand grip strength measured (in kilograms) with a hand dynamometer. A higher result means a better performance.	The test will be repeated at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.
Secondary	Activities of Daily Living (ADL) index score	Minimum score: 0, maximum score: 6, a higher score means a better performance.	The score will be taken at Day 0 Screening visit, at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups..
Secondary	Instrumental Activities of Daily Living (IADL) scale score	Minimum score: 0, maximum score: 8, a higher score means a better performance.	The score will be taken at Day 0 Screening visit, at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.
Secondary	Barthel Index score	Minimum score: 0, maximum score: 100, a higher score means a better performance.	The score will be taken at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.
Secondary	14-item Resilience Scale (RS-14) score	Minimum score: 14, maximum score: 98, a higher score means a better outcome.	The score will be taken at baseline, at Month 6, Month 12, and Month 18 follow-ups.
Secondary	Number of falls taken	A higher number of falls means a worse outcome.	Through study completion, an average of 2 years.
Secondary	Number of hospital admissions	A higher number of hospital admissions means a worse outcome.	Through study completion, an average of 2 years.
Secondary	Number of visits to general practitioner	The number does not indicate a better or worse outcome. It is only informative.	Through study completion, an average of 2 years.
Secondary	Geriatric Depression Scale (GDS) score	Minimum: 0, maximum: 15, a higher score indicates a worse outcome.	The score will be taken at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.
Secondary	UCLA Loneliness Scale (UCLA-LS) score	Minimum: 20, maximum: 80, a higher score indicates a worse outcome.	The score will be taken at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.
Secondary	Psychological General Well Being Index (PGWBI) score	Minimum: 0, maximum: 110, a higher score indicates a worse outcome.	The score will be taken at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.
Secondary	World Health Organization Quality Of Life Questionnaire - Brief (WHO-QOL-Brief) score - Physical Health	Minimum: 0, maximum: 100, a higher score means a better outcome.	The score will be taken at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.
Secondary	World Health Organization Quality Of Life Questionnaire - Brief (WHO-QOL-Brief) score - Psychological Health	Minimum: 0, maximum: 100, a higher score means a better outcome.	The score will be taken at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.
Secondary	World Health Organization Quality Of Life Questionnaire - Brief (WHO-QOL-Brief) score - Social Relationships	Minimum: 0, maximum: 100, a higher score means a better outcome.	The score will be taken at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.
Secondary	World Health Organization Quality Of Life Questionnaire - Brief (WHO-QOL-Brief) score - Environment	Minimum: 0, maximum: 100, a higher score means a better outcome.	The score will be taken at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.
Secondary	World Health Organization Quality Of Life Questionnaire - Brief (WHO-QOL-Brief) score - Quality of Life	Minimum: 1, maximum: 5, a higher score means a better outcome.	The score will be taken at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.
Secondary	World Health Organization Quality Of Life Questionnaire - Brief (WHO-QOL-Brief) score - Health Satisfaction	Minimum: 1, maximum: 5, a higher score means a better outcome.	The score will be taken at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.
Secondary	Pittsburgh Sleep Quality Index (PSQI) score	Minimum: 0, maximum: 21, a higher score means a worse outcome.	The score will be taken at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.
Secondary	Mini Nutritional Assessment-Short Form (MNA-SF) score	Minimum: 0, maximum: 14, a higher score means a better outcome.	The score will be taken at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.
Secondary	Mediterranean Diet Scale (MDScale) score	Minimum: 0, maximum: 9, a higher score means a better outcome.	The score will be taken at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.
Secondary	Framingham Risk Score	Measured in percentage %, 0-100%. A higher percentage indicates a higher cardiovascular risk (worse outcome).	The score will be taken at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.
Secondary	Cognitive Reserve Index questionnaire (CRIq) score	z-score without a maximum or minimum value, a higher z-score means a better outcome.	The score will be taken at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.
Secondary	Intrinsic Motivation Inventory (IMI) score	Minimum: 45, maximum: 315, a higher score means a better outcome.	The score will be taken at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.
Secondary	Number of incidental diagnoses of Mild Cognitive Impairment (MCI) and dementia, according to National Institute on Aging-Alzheimer's Association (NIA-AA) criteria	A higher number means a worse outcome.	Through study completion, an average of 2 years.
Secondary	Composite score of processing speed and attention	z-score without a maximum or minimum value, a higher z-score means a better outcome.	The score will be taken at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.
Secondary	Composite score of executive functions	z-score without a maximum or minimum value, a higher z-score means a better outcome.	The score will be taken at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.
Secondary	Composite memory score	z-score without a maximum or minimum value, a higher z-score means a better outcome.	The score will be taken at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.
Secondary	Composite language score	z-score without a maximum or minimum value, a higher z-score means a better outcome.	The score will be taken at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.
Secondary	Composite score of general cognitive assessment	z-score without a maximum or minimum value, a higher z-score means a better outcome.	The score will be taken at Baseline visit (Day 0 of second phase, which should be indicatively within 30 days of Screening visit), at Month 6, Month 12, and Month 18 follow-ups.