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

Primary Purpose

Cognitive Impairment, Alzheimer Disease, Vascular Cognitive Impairment

Status
Recruiting
Phase
Not Applicable
Locations
Singapore
Study Type
Interventional
Intervention
Structured Lifestyle Intervention
Self-Guided Intervention
Sponsored by
National University of Singapore
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Cognitive Impairment focused on measuring cognitive decline, cognitive impairment, multi-domain lifestyle interventions, dementia, elderly

Eligibility Criteria

60 Years - 77 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • National University HospitalRecruiting
  • National University of Singapore, Yong Loo Lin School of MedicineRecruiting
  • National Neuroscience Institute @ Tan Tock Seng Campus (NNI @ TTSH campus)

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Structured Lifestyle Intervention

Self-Guided Intervention

Arm Description

Structured lifestyle modification program developed for participants targeting diet, physical exercise, cognitive training, and social stimulation.

General health information provided to participants.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Executive Function
Executive function measured using mNTB subtests: Digit Span, Word and Category Fluency test, Trail Making Test Part B.
Processing Speed
Processing speed measured using mNTB subtests: Letter Digit Substitution test and Trail-Making Test Part A.
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.
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.
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.
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'.
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.
Pittsburgh Sleep Quality Index (PSQI)
The Pittsburgh Sleep Quality Index (PSQI) is scored from 0 to 21. Higher scores indicate worse sleep quality.
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.
Physical Performance Test (PPT)
The Physical Performance Test (PPT) is scored from 0 to 36. Higher scores represent better performance.
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.
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.
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.
Height
Height is measured in metres.
Weight
Weight is measured in kilograms.
Hip and waist circumference
Hip and waist circumference measured in centimetres.
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.
Changes in Lipid Profile
Vascular and metabolic risk factors measured by changes in lipid profile in mmol/L.
Changes in Glucose Regulation
Vascular and metabolic risk factors measured by changes in glucose regulation in mmol/L.
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.
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 Aβ, tau and synaptic pathology, oxidative stress, endothelial/cardiovascular injury and degenerative protein modifications (DPMs) damaged proteins will be used.
Retinal Imaging Markers
Multimodal retinal imaging will be used to assess retinal structural, vascular and neuronal changes.

Full Information

First Posted
July 28, 2021
Last Updated
August 23, 2021
Sponsor
National University of Singapore
Collaborators
National Medical Research Council (NMRC), Singapore
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1. Study Identification

Unique Protocol Identification Number
NCT05007353
Brief Title
The SINgapore GERiatric Intervention Study to Reduce Cognitive Decline and Physical Frailty (SINGER) Study
Acronym
SINGER
Official Title
The SINgapore GERiatric Intervention Study to Reduce Cognitive Decline and Physical Frailty (SINGER) Study, Biomarker and Health Service Research Analyses
Study Type
Interventional

2. Study Status

Record Verification Date
August 2021
Overall Recruitment Status
Recruiting
Study Start Date
August 23, 2021 (Actual)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
January 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
National University of Singapore
Collaborators
National Medical Research Council (NMRC), Singapore

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cognitive Impairment, Alzheimer Disease, Vascular Cognitive Impairment, Dementia, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Neurocognitive Disorders, Mental Disorders, Cognition Disorder
Keywords
cognitive decline, cognitive impairment, multi-domain lifestyle interventions, dementia, elderly

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
1200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Structured Lifestyle Intervention
Arm Type
Experimental
Arm Description
Structured lifestyle modification program developed for participants targeting diet, physical exercise, cognitive training, and social stimulation.
Arm Title
Self-Guided Intervention
Arm Type
Experimental
Arm Description
General health information provided to participants.
Intervention Type
Behavioral
Intervention Name(s)
Structured Lifestyle Intervention
Other Intervention Name(s)
SLI
Intervention Description
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.
Intervention Type
Behavioral
Intervention Name(s)
Self-Guided Intervention
Other Intervention Name(s)
SGI
Intervention Description
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.
Primary Outcome Measure Information:
Title
Global Cognition
Description
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.
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Episodic Memory
Description
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.
Time Frame
Up to 2 years
Title
Executive Function
Description
Executive function measured using mNTB subtests: Digit Span, Word and Category Fluency test, Trail Making Test Part B.
Time Frame
Up to 2 years
Title
Processing Speed
Description
Processing speed measured using mNTB subtests: Letter Digit Substitution test and Trail-Making Test Part A.
Time Frame
Up to 2 years
Title
Clinical Dementia Rating-Sum of Boxes (CDR-SB)
Description
The Clinical Dementia Rating-Sum of Boxes (CDR-SB) is scored from 0 to 18. Higher scores reflect worse performance.
Time Frame
Up to 2 years
Title
Alzheimer's Disease Cooperative Study Activities of Daily Living-Mild Cognitive Impairment-Activities of Daily Living Inventory (ADCS-MCI-ADL)
Description
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.
Time Frame
Up to 2 years
Title
The Geriatric Depression Scale (GDS)
Description
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.
Time Frame
Up to 2 years
Title
Global Physical Activity Questionnaire (GPAQ)
Description
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'.
Time Frame
Up to 2 years
Title
Prospective-Retrospective Memory Questionnaire
Description
The Prospective-Retrospective Memory Questionnaire (PRMQ) is measured on a 5-point scale. Higher scores represent greater frequency of memory failures.
Time Frame
Up to 2 years
Title
Pittsburgh Sleep Quality Index (PSQI)
Description
The Pittsburgh Sleep Quality Index (PSQI) is scored from 0 to 21. Higher scores indicate worse sleep quality.
Time Frame
Up to 2 years
Title
Leisure-Time Activities Questionnaire
Description
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.
Time Frame
Up to 2 years
Title
Physical Performance Test (PPT)
Description
The Physical Performance Test (PPT) is scored from 0 to 36. Higher scores represent better performance.
Time Frame
Up to 2 years
Title
Quality of Life Questionnaire (15D)
Description
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.
Time Frame
Up to 2 years
Title
36-Item Short Form Survey (SF-36)
Description
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.
Time Frame
Up to 2 years
Title
Resource Use Inventory (RUI)
Description
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.
Time Frame
Up to 2 years
Title
Height
Description
Height is measured in metres.
Time Frame
Up to 2 years
Title
Weight
Description
Weight is measured in kilograms.
Time Frame
Up to 2 years
Title
Hip and waist circumference
Description
Hip and waist circumference measured in centimetres.
Time Frame
Up to 2 years
Title
Changes in Blood Pressure
Description
Vascular and metabolic risk factors measured by changes in blood pressure in mmHg. Incident events using serious adverse event reports will also be assessed.
Time Frame
Up to 2 years
Title
Changes in Lipid Profile
Description
Vascular and metabolic risk factors measured by changes in lipid profile in mmol/L.
Time Frame
Up to 2 years
Title
Changes in Glucose Regulation
Description
Vascular and metabolic risk factors measured by changes in glucose regulation in mmol/L.
Time Frame
Up to 2 years
Title
Neuroimaging
Description
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.
Time Frame
Up to 2 years
Title
Blood Biomarkers
Description
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 Aβ, tau and synaptic pathology, oxidative stress, endothelial/cardiovascular injury and degenerative protein modifications (DPMs) damaged proteins will be used.
Time Frame
Up to 2 years
Title
Retinal Imaging Markers
Description
Multimodal retinal imaging will be used to assess retinal structural, vascular and neuronal changes.
Time Frame
Baseline only

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
77 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Connie KL Teo
Phone
(65) 6601 5668
Email
kee_ling_teo@nuhs.edu.sg
First Name & Middle Initial & Last Name or Official Title & Degree
April KS Phua
Phone
(65) 6601 5668
Email
aprilphua@nuhs.edu.sg
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christopher LH Chen, MD
Organizational Affiliation
National University of Singapore
Official's Role
Principal Investigator
Facility Information:
Facility Name
National University Hospital
City
Singapore
ZIP/Postal Code
117600
Country
Singapore
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Connie Teo
Phone
(65) 6601 5668
Email
kee_ling_teo@nuhs.edu.sg
First Name & Middle Initial & Last Name & Degree
Christopher LH Chen, MD
First Name & Middle Initial & Last Name & Degree
Effie Chew, MD
First Name & Middle Initial & Last Name & Degree
Chester Drum, MD, PhD
First Name & Middle Initial & Last Name & Degree
Dave YH Lee, MD
First Name & Middle Initial & Last Name & Degree
Mingchang Wang, MD
Facility Name
National University of Singapore, Yong Loo Lin School of Medicine
City
Singapore
ZIP/Postal Code
117600
Country
Singapore
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Connie Teo
Phone
(65) 6601 5668
Email
kee_ling_teo@nuhs.edu.sg
First Name & Middle Initial & Last Name & Degree
Christopher LH Chen, MD
First Name & Middle Initial & Last Name & Degree
Christiani J Henry, PhD
First Name & Middle Initial & Last Name & Degree
Josip Car, MD, PhD
First Name & Middle Initial & Last Name & Degree
Juan H Zhou, PhD
First Name & Middle Initial & Last Name & Degree
Mark Richards, MD, PhD, Dsc
First Name & Middle Initial & Last Name & Degree
Mitchell Lai, PhD
First Name & Middle Initial & Last Name & Degree
Jianjun Liu, PhD
Facility Name
National Neuroscience Institute @ Tan Tock Seng Campus (NNI @ TTSH campus)
City
Singapore
ZIP/Postal Code
308433
Country
Singapore
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yi Jin Leow
Phone
+65-6357 7613
Email
Yi_Jin_Leow@nni.com.sg
First Name & Middle Initial & Last Name & Degree
Benjamin Wong
Phone
+65-6357 7613
Email
Benjamin_WONG@nni.com.sg
First Name & Middle Initial & Last Name & Degree
Nagaendran Kandiah, MD
First Name & Middle Initial & Last Name & Degree
John Chambers, PhD

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Interested collaborators may put in a request.
Citations:
PubMed Identifier
25771249
Citation
Ngandu T, Lehtisalo J, Solomon A, Levalahti E, Ahtiluoto S, Antikainen R, Backman L, Hanninen T, Jula A, Laatikainen T, Lindstrom 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.
Results Reference
background
PubMed Identifier
33748399
Citation
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.
Results Reference
background

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

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