The SINgapore GERiatric Intervention Study to Reduce Cognitive Decline and Physical Frailty (SINGER) Study

Alzheimer Disease Clinical Trial

— SINGER  

Official title:

The SINgapore GERiatric Intervention Study to Reduce Cognitive Decline and Physical Frailty (SINGER) Study, Biomarker and Health Service Research Analyses

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05007353
• Other study ID #: SINGER 2021
• Status: Recruiting
• Phase: N/A
• Start date: August 23, 2021
• Est. completion date: January 31, 2026

Study information

• Verified date: August 2021
• Source: National University, Singapore
• Contact: Connie KL Teo
• Phone: (65) 6601 5668
• Email: kee_ling_teo[@]nuhs.edu.sg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A study in Finland found that a multidomain intervention of physical activity, nutritional guidance, cognitive training, social activities and management of vascular risk factors slowed cognitive decline in healthy older adults at increased risk of cognitive decline. A 6-month pilot study was initiated in Singapore, which demonstrated the cultural feasibility and practicality of the FINGER interventions and a set of locally adapted interventions in an Asian population. The SINGER study is a 2-year randomized controlled trial that aims to test the efficacy and safety of these lifestyle changes, including diet and cardiovascular risk factor management, cognitive and physical exercises, in delaying cognitive decline in older adults at risk of dementia.

Description:

Results from a population-based 2-year clinical trial, the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), demonstrated that a multidomain intervention of physical activity, nutritional guidance, cognitive training, social activities and management of vascular risk factors slowed cognitive decline in healthy older adults at increased risk of cognitive decline. Currently, no pharmacological treatment options that can rival these effects. Thus, there is an urgent need to test the generalizability, adaptability, and sustainability of these findings in Singaporean populations. A 6-month pilot study was initiated in Singapore, which demonstrated the cultural feasibility and practicality of the FINGER interventions and a set of locally adapted interventions in an Asian population. Hence, the next step was to conduct a larger scale SINGER trial to determine the efficacy of these interventions in Singapore. If the interventions are found to be effective and safe with high applicability and scalability, the study will provide important clinical and public health implications to a rapidly increasing ageing population.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1200
• Est. completion date: January 31, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 60 Years to 77 Years

Eligibility

Inclusion Criteria:

• Age 60-77 years

• Able to understand English/Chinese

• Risk of dementia: Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) dementia risk score >6 indicating the presence of modifiable risk factors Modifiable lifestyle factors (fulfilling at least one of the following LIBRA index for diet, cognitive activity, physical activity)

• Cognitive performance at the mean level or slightly lower than expected for age (MoCA =18, =27)

• No plans to travel outside of Singapore for an extended period of time over the course of the study

• Free of physical disabilities that preclude participation in the study

• Willing to complete all study-related activities for 24 months

• Willing to be randomized to either lifestyle intervention group

Exclusion Criteria:

• malignant diseases

• dementia

• substantial cognitive decline (MoCA<18)

• major depression

• symptomatic cardiovascular disease

• revascularisation within 1 year

• severe loss of vision, hearing or communicative ability

• other conditions inhibiting from safe engagement in the prescribed intervention and other conditions preventing cooperation, as judged by the study physician

Related Conditions & MeSH terms

• Alzheimer Disease
• Brain Diseases
• Central Nervous System Diseases
• Cognition Disorder
• Cognition Disorders
• Cognitive Dysfunction
• Cognitive Impairment
• Dementia
• Disease
• Frailty
• Mental Disorders
• Nervous System Diseases
• Neurocognitive Disorders
• Vascular Cognitive Impairment

Intervention

Behavioral:
• Structured Lifestyle Intervention
Structured Lifestyle Intervention (SLI) involves providing participants with intensive structure and support by a team of trainers to increase physical exercise, adhere to a healthy diet, cognitive training, increase intellectual/social stimulation, and better manage vascular risk factors.
• Self-Guided Intervention
In the Self-Guided Intervention (SGI), education about the importance of a healthy lifestyle as a preventive strategy and support to encourage change will be provided.

Locations

Country	Name	City	State
Singapore	National Neuroscience Institute @ Tan Tock Seng Campus (NNI @ TTSH campus)	Singapore
Singapore	National University Hospital	Singapore
Singapore	National University of Singapore, Yong Loo Lin School of Medicine	Singapore

Sponsors (2)

Lead Sponsor	Collaborator
National University, Singapore	National Medical Research Council (NMRC), Singapore

Country where clinical trial is conducted

Singapore, 

References & Publications (2)

Chew KA, Xu X, Siongco P, Villaraza S, Phua AKS, Wong ZX, Chung CY, Tang N, Chew E, Henry CJ, Koo E, Chen C. SINgapore GERiatric intervention study to reduce physical frailty and cognitive decline (SINGER)-pilot: A feasibility study. Alzheimers Dement (N Y). 2021 Mar 15;7(1):e12141. doi: 10.1002/trc2.12141. eCollection 2021. — View Citation

Ngandu T, Lehtisalo J, Solomon A, Levälahti E, Ahtiluoto S, Antikainen R, Bäckman L, Hänninen T, Jula A, Laatikainen T, Lindström J, Mangialasche F, Paajanen T, Pajala S, Peltonen M, Rauramaa R, Stigsdotter-Neely A, Strandberg T, Tuomilehto J, Soininen H, Kivipelto M. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet. 2015 Jun 6;385(9984):2255-63. doi: 10.1016/S0140-6736(15)60461-5. Epub 2015 Mar 12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Global Cognition	Global cognition measured using the modified Neuropsychological Test Battery (mNTB) that includes: Visual Paired Associates, Logical Memory Recall of the Wechsler Memory Scale-Revised, Rey Auditory Verbal Learning, Digit Span, Word and Category Fluency test, Trail Making Test, Letter Digit Substitution test.	Up to 2 years
Secondary	Episodic Memory	Episodic memory measured using mNTB subtests: Visual paired associates tests, Logical Memory immediate and delayed recall of the Wechsler Memory Scale-Revised, Rey Auditory Verbal Learning test.	Up to 2 years
Secondary	Executive Function	Executive function measured using mNTB subtests: Digit Span, Word and Category Fluency test, Trail Making Test Part B.	Up to 2 years
Secondary	Processing Speed	Processing speed measured using mNTB subtests: Letter Digit Substitution test and Trail-Making Test Part A.	Up to 2 years
Secondary	Clinical Dementia Rating-Sum of Boxes (CDR-SB)	The Clinical Dementia Rating-Sum of Boxes (CDR-SB) is scored from 0 to 18. Higher scores reflect worse performance.	Up to 2 years
Secondary	Alzheimer's Disease Cooperative Study Activities of Daily Living-Mild Cognitive Impairment-Activities of Daily Living Inventory (ADCS-MCI-ADL)	The Alzheimer's Disease Cooperative Study Activities of Daily Living-Mild Cognitive Impairment-Activities of Daily Living Inventory (ADCS-MCI-ADL) is scored from 0 to 53. Higher scores reflect better performance.	Up to 2 years
Secondary	The Geriatric Depression Scale (GDS)	The Geriatric Depression Scale (GDS) is scored from 0 to 15. Scores of 0-4 are considered normal, 5-8 indicate mild depression; 9-11 indicate moderate depression; and 12-15 indicate severe depression.	Up to 2 years
Secondary	Global Physical Activity Questionnaire (GPAQ)	The Global Physical Activity Questionnaire (GPAQ) measures physical activity across 3 domains: work, travel, and recreation, as well as average time per day spent in sedentary behavior. The GPAQ is scored based on a population's mean or median physical activity spent in physical activity or by classifying a certain percentage of a population as 'inactive' or 'insufficiently active'.	Up to 2 years
Secondary	Prospective-Retrospective Memory Questionnaire	The Prospective-Retrospective Memory Questionnaire (PRMQ) is measured on a 5-point scale. Higher scores represent greater frequency of memory failures.	Up to 2 years
Secondary	Pittsburgh Sleep Quality Index (PSQI)	The Pittsburgh Sleep Quality Index (PSQI) is scored from 0 to 21. Higher scores indicate worse sleep quality.	Up to 2 years
Secondary	Leisure-Time Activities Questionnaire	The Leisure-Time Activities Questionnaire measures the frequency of engagement in the following activities: Health activities, Social activities, Productive activities, Fitness activities, Recreational activities, Any cognitively-stimulating activities. Scores are measured on a 3-point scale. Higher scores represent higher frequency of engagement in leisure-time activities.	Up to 2 years
Secondary	Physical Performance Test (PPT)	The Physical Performance Test (PPT) is scored from 0 to 36. Higher scores represent better performance.	Up to 2 years
Secondary	Quality of Life Questionnaire (15D)	The Quality of Life Questionnaire (15D) has a single index (15D score) on a 0-1 scale, which represents overall HRQoL (0 = being dead, 0.0162 = being unconscious or comatose, 1 = no problems on any dimension = 'full' HRQOL). This is calculated from the health state descriptive system by using a set of population-based preference or utility weights.	Up to 2 years
Secondary	36-Item Short Form Survey (SF-36)	The 36-Item Short Form Survey (SF-36) has eight domains. Each domain is scored from 0 to 100. Higher scores represent a more favourable health state.	Up to 2 years
Secondary	Resource Use Inventory (RUI)	The Resource Use Inventory (RUI) measures 4 domains: direct medical care, direct nonmedical care, informal care, and subjects' time use. The RUI is filled in based on the frequency and amount of resources used. If none were used, '00' is entered.	Up to 2 years
Secondary	Height	Height is measured in metres.	Up to 2 years
Secondary	Weight	Weight is measured in kilograms.	Up to 2 years
Secondary	Hip and waist circumference	Hip and waist circumference measured in centimetres.	Up to 2 years
Secondary	Changes in Blood Pressure	Vascular and metabolic risk factors measured by changes in blood pressure in mmHg. Incident events using serious adverse event reports will also be assessed.	Up to 2 years
Secondary	Changes in Lipid Profile	Vascular and metabolic risk factors measured by changes in lipid profile in mmol/L.	Up to 2 years
Secondary	Changes in Glucose Regulation	Vascular and metabolic risk factors measured by changes in glucose regulation in mmol/L.	Up to 2 years
Secondary	Neuroimaging	Magnetic Resonance Imaging will be used to assess changes in brain structural integrity, grey matter volume loss, white matter microstructure degradation, and increase of cerebrovascular disease markers (CeVD). Vascular polygenic risk scores (PRS) and its association with neurodegeneration, CeVD burden and cognitive decline will be performed.	Up to 2 years
Secondary	Blood Biomarkers	Novel and accessible blood markers to monitor AD- and CeVD-associated pathologies will be measured. Plasma concentrations of cardiac markers (High-sensitive cardiac troponin T (hs Troponin T), N-terminal pro b-type natriuretic peptide (NT-proBNP) and Growth/differentiation factor 15 (GDF 15)), and peripheral biomarkers of Aß, tau and synaptic pathology, oxidative stress, endothelial/cardiovascular injury and degenerative protein modifications (DPMs) damaged proteins will be used.	Up to 2 years
Secondary	Retinal Imaging Markers	Multimodal retinal imaging will be used to assess retinal structural, vascular and neuronal changes.	Baseline only