CLEVER: Cognitive Level Enhancement Through Vision Exams and Refraction

Sponsor

Queen's University, Belfast (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05458323

Collaborator

L.V. Prasad Eye Institute (Other), National Institute of Mental Health and Neuro Sciences, India (Other), The George Institute (Other), Johns Hopkins University (Other), University of Michigan (Other), Clearly (Other), Belfast Health and Social Care Trust (Other)

760

Enrollment

Location

Arms

Anticipated Duration (Months)

15.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The investigators aim to conduct a mixed-method study in which a randomised controlled trial (RCT) and a descriptive qualitative study will be conducted. The RCT aims to determine whether free near and distance glasses provided to residents in Hyderabad, India, aged ≥ 60 years, with under- or un- corrected refractive error and normal baseline hearing and cognition (HMSE > 18), can improve quality of life, reduce falls, reduce depression, improve social interaction and physical activity cost-effectively over 36 months. The primary qualitative research aim is to a) contextualize the RCT with information on the milieu and culture in which the trial will be conducted; b) provide data on the lived experiences of older adults with reduced vision in the study area, and c) conduct a process evaluation of the trial.

The primary outcome measure is the three-year change in cognition measured by LASI- DAD (Longitudinal Aging Study in India(LASI)- Diagnostic Assessment of Dementia(DAD) global cognitive score.

Secondary Outcome Measures:

Domain-specific cognitive function (orientation, executive function, language/fluency, memory), quality of life (WHOQOL BREF), self-reported visual functioning (INDVFQ), falls, mobility, depression (PHQ9), glasses compliance, cost-effectiveness (total intervention cost per additional quality-adjusted life years(QALY) gained in the intervention group), social interaction/isolation (Social Networking Index, SNI), self-reported physical activity (GPAQ). An additional secondary outcome will be LASI-DAD global cognitive score analysed by excluding any tests determined pre-hoc to depend on visual acuity.

Condition or Disease	Intervention/Treatment	Phase
Refractive Errors	Device: Free near and Distance Vision glasses	N/A

Detailed Description

The number of people living with dementia globally will rise from 50 million in 2017 to 131.5 million by 2050. The majority reside in low and middle-income countries (LMICs), where a 223% increase in the burden of dementia is expected from 2015 to 2050. The household cost of caring for demented relatives in India was £2.48 billion in 2013, where total expenses for dementia care will soon consume 0.5% of Gross Domestic Product (GDP). Despite the rapidly-growing burden of dementia in India, only 1 in 10 affected are diagnosed or treated. Proven preventive strategies are desperately needed to close the gap, and could reduce incidence by an estimated 41%, especially early, at the stage of mild cognitive impairment, which itself increases risk of dementia by 23-fold. Existing interventions have predominantly been evaluated in high-income countries (HIC), despite the acknowledged need for prevention in low resource settings. India's national dementia strategy, documented in the Alzheimer's and Related Society of India (ARDSI) Report (2018) and Dementia in India (2020), echo the WHO Dementia Global Action Plan (2017) in prioritising evidence-based approaches to reduce risk.

The elderly, at greatest risk for cognitive disorders, also have the highest prevalence of vision impairment, which affects 2.2 billion persons globally. Growing longitudinal evidence links vision impairment and risk of cognitive decline, with population studies in the United States reporting a 55% increased 9-year risk of new cognitive impairment among visually impaired persons. Longitudinal studies elsewhere in the United States, France, Singapore and China report similar results. While vision impairment is a strong predictor of future cognitive performance, cognition is relatively weakly linked to future visual decline. Both distance impairment and impairment of near vision, a nearly universal part of aging without refractive correction, have been implicated. Observational studies also suggest vision care slows rates of cognitive decline by up to 50%. The association between vision loss and cognitive decline and dementia, while consistent and strong, is not well understood, and various causal pathways have been posited. These include common neurodegenerative or micro vascular aetiology, increased cognitive load, and limited social contact and physical activity due to poor vision, each independently shown to elevate risk of dementia. Studies investigating the role of vision correction in slowing cognitive decline will have a significant impact in developing strategies to reduce the burden of dementia.

Design: single centre, open label, two-arm, parallel group, stratified, interventional randomised trial with a qualitative component Rationale: Despite considerable longitudinal observational evidence, there have been no randomised trials to investigate whether providing near and distance glasses can slow cognitive decline in the elderly. Proof of a causative association between vision correction and the slowing of cognitive decline is needed to potentiate investment in inexpensive vision care for prevention. This requires randomised trials, and none have yet been done.

Study Plan:

Eligibility assessments conducted for 1300 participants. After providing the consent and meeting the eligibility criteria, 760 participants randomised to intervention and control groups.

Annual follow-ups for 3 years for both groups. Lost to follow ups documented with reason for both groups. Missed data for both groups analysed as intention to treat (ITT) and will be excluded from analysis with reasons documented.

Primary outcomes: Three-year change in cognition measured by LASI-DAD global cognitive score.

Secondary Outcome Measures: Domain-specific cognitive function (orientation, executive function, language/fluency, memory), quality of life (WHOQOL BREF), self-reported visual functioning (INDVFQ), falls, mobility, depression (PHQ9), glasses compliance, cost-effectiveness (total intervention cost per additional QALY gained in the intervention group), social interaction/isolation (Social Networking Index, SNI), self-reported physical activity (GPAQ). An additional secondary outcome will be LASI-DAD global cognitive score analysed by excluding any tests determined pre-hoc to depend on visual acuity.

Hindi Mental State Examination, Medical history and comorbidity questionnaire, Hearing Questionnaire, Client Services Receipt Inventory.

Statistical methods: The primary analysis will use a significance level of <0.05 and will compare the change in LASI-DAD global cognitive score (primary outcome, with sensitivity analysis including and excluding vision-dependent tests) between groups using a 2-sample t-test. Both the raw comparison, and the comparison adjusting for potential determinants of change in cognitive status, such as baseline cognitive score, age, sex and education (further covariates will be detailed in the SAP) using general linear models. Similar methods will be used for other time-points and secondary outcomes that are continuous data.

Justification for sample size: Imputing three-year un-intervened decline in the outcome variable (LASI-DAD global score from cross-sectional, age-stratified data17, at 29% effect size (from the ACHIEVE study), 502 participants give 90% power at p = 0.05 (two-tailed) based on a two-sample test. With annual follow-up loss of 13% based on estimation from previous studies done in India, 760 total participants are needed across the two study groups. With 60% prevalence of uncorrected distance and/or near refractive error, the total number of people needing to be screened is estimated at approximately 1300.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

760 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

CLEVER is a single centre, open label, 2-arm, parallel group, stratified, interventional randomised trial, with allocation ratio of 1:1 powered to test superiority of the impact of providing spectacles on rates of cognitive decline among older adults.CLEVER is a single centre, open label, 2-arm, parallel group, stratified, interventional randomised trial, with allocation ratio of 1:1 powered to test superiority of the impact of providing spectacles on rates of cognitive decline among older adults.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Cognitive Level Enhancement Through Vision Exams and Refraction: a Randomized Controlled Trial to Assess Impact of Near and Distance Spectacles on Reducing Rates of Cognitive Decline With Aging in Community Dwelling Older People in India

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

Aug 1, 2025

Anticipated Study Completion Date :

Sep 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Free near and distance glasses All participants randomised to the intervention group will be provided with free near and/or distance spectacles based on the results of refraction. The participants will be asked to choose from an assortment of 20 frames. Participants will be asked to report to the project coordinator in case of any issue with spectacles or if spectacles are lost or broken. Replacement glasses will be provided in case of broken or lost spectacles whenever required. Participants will undergo annual eye exams and refraction, and change of glasses will be prescribed as needed.	Device: Free near and Distance Vision glasses Intervention Description: All participants randomised to the intervention group will be provided with free near and/or distance spectacles based on the results of refraction.
No Intervention: Control-No treatment All participants randomised to the control group will receive a prescription for spectacles and given free near and/or distance glasses as needed at study close out.

Arm

Intervention/Treatment

Experimental: Free near and distance glasses

All participants randomised to the intervention group will be provided with free near and/or distance spectacles based on the results of refraction. The participants will be asked to choose from an assortment of 20 frames. Participants will be asked to report to the project coordinator in case of any issue with spectacles or if spectacles are lost or broken. Replacement glasses will be provided in case of broken or lost spectacles whenever required. Participants will undergo annual eye exams and refraction, and change of glasses will be prescribed as needed.

Device: Free near and Distance Vision glasses

Intervention Description: All participants randomised to the intervention group will be provided with free near and/or distance spectacles based on the results of refraction.

No Intervention: Control-No treatment

All participants randomised to the control group will receive a prescription for spectacles and given free near and/or distance glasses as needed at study close out.

Outcome Measures

Primary Outcome Measures

Change in cognitive score [Time point(s) of primary interest: 36 months collected at 12, 24 and 36 months]
The metric or method of measurement to be used: LASI-DAD global cognitive score. The best possible score is 360 and the worst possible score is 0.

Secondary Outcome Measures

26-Item Quality of Life [Time point(s) of primary interest: 36 months collected every 12 months - ie at 12, 24 and 36 months]
The metric or method of measurement to be used: Quality of Life using WHO BREF questionnaire. Higher scores (for 4 domains) indicate higher quality of life and vice versa (it is a continuum)
Cost effectiveness [Time point(s) of primary interest: 36 months collected every 12 months - ie at 12, 24 and 36 months]
The metric or method of measurement to be used: Cost-effectiveness using Client Service Receipt Inventory
Social interaction/isolation [Time point(s) of primary interest: 36 months collected every 12 months - ie at 12, 24 and 36 months]
The metric or method of measurement to be used: Social Networking Index. The best possible score is 12 and the worst possible score is 0
Self-reported physical activity. [Time point(s) of primary interest: 36 months collected every 12 months - ie at 12, 24 and 36 months]
The metric or method of measurement to be used: Global Physical Activity Questionnaire Self-reported physical activity: Global Physical Activity Questionnaire (GPAQ).
Falls [Time point(s) of primary interest: 36 months collected every 12 months - ie at 12, 24 and 36 months]
The metric or method of measurement to be used: Quick Screen for falls Risk. The worst possible score is 7% and the best possible score is 49%
Depression [Time point(s) of primary interest: 36 months collected every 12 months - ie at 12, 24 and 36 months]
The metric or method of measurement to be used: Patient Health Questionnaire, PHQ9. Worst score is 0 and best possible score is 27
Glasses compliance [Time point(s) of primary interest: 36 months collected every 12 months - ie at 12, 24 and 36 months]
The metric or method of measurement to be used: Use of glasses during follow-up visits. The best possible score is 1 and the worst possible score is 0
Visual Function [Time point(s) of primary interest: 36 months collected every 12 months - ie at 12, 24 and 36 months]
The metric or method of measurement to be used: Indian VFQ. The measure will be in logits (using Rasch-scaled interval scores) and it is a continuum with positive person scores indicating lower visual functioning and negative scores indicating better visual functioning.
Domain-specific cognitive function [Time point(s) of primary interest: 36 months collected every 12 months - ie at 12, 24 and 36 months]
The metric or method of measurement to be used: Hindi Mental State Examination. The best possible score is 31 and the worst possible score is 0.

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Community dwelling
Residency

Participants must plan to reside in the local area for the study duration

Presenting vision in the better eye due to uncorrected refractive error
Impaired distance vision less than 6/12
Near vision less than N8 at 40 cm
Presenting vision in the better eye due to under-corrected refractive error
Impaired distance vision less than 6/12
Near vision less than N8 at 40 cm
Willingness
to participate
to be randomized
to adhere to the protocol

Exclusion criteria

Impaired baseline cognition

HMSE score less than or equal to 18

Non-refractive causes of vision impairment
Severely impaired mobility
immobile
bedridden
wheelchair
using walker
Severe medical illness likely to limit the life span
Cancer
Heart disease
Stroke
HIV or AIDS
Chronic lung disease
Kidney disease
Hearing loss assessment
self-reported hearing impairment
inability to hear
inability to repeat short phrases in local languages

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	L V Prasad Eye Institute	Hyderabad	Telangana	India	500086

Sponsors and Collaborators

Queen's University, Belfast
L.V. Prasad Eye Institute
National Institute of Mental Health and Neuro Sciences, India
The George Institute
Johns Hopkins University
University of Michigan
Clearly
Belfast Health and Social Care Trust

Investigators

Principal Investigator: Nathan G Congdon, MD, MPH, Queen's University, Belfast
Principal Investigator: Rohit C Khanna, MPH, L.V. Prasad Eye Institute
Principal Investigator: Suvarna Alladi, DM, National Institute of Mental Health and Neuro Sciences, India