Clinical trial NCT05458323: Cognitive Level Enhancement Through Vision Exams and Refraction
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Refractive Errors
Keywords: Cognitive Decline
Elderly
Refractive Error
Spectacles
cost effectiveness analysis
dementia
Lead sponsor: Queen's University, Belfast
Sponsor class: OTHER
Collaborators: name: L.V. Prasad Eye Institute
name: National Institute of Mental Health and Neuro Sciences, India
name: The George Institute
name: Johns Hopkins University
name: University of Michigan
name: Clearly
name: Belfast Health and Social Care Trust
First posted: 2022-07-14
Enrollment: 760
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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: Three year change in Quality of Life score measured by WHO QOL-BREF; Visual functioning from the RASCH-scaled version of INDVFQ(Indian Visual Functioning(INDVFQ);self-reported physical activity score measured using IPAQ questionnaire; PHQ9 score; domain specific cognitive score (orientation, executive function, language/fluency, memory) measured by HMSE; Total cost of care including direct and indirect costs; Quality adjusted life years; Incremental Cost Effectiveness Ratio; Number of falls measured by Quick Screen score over the three years; Social network density at 3 years (SNI 1-3 represents a "limited" social network, 4-5 is a "medium" social network, and SNI ≥6 is a "diverse" social network) measured by the SNI score; An additional secondary outcome will be LASI-DAD global cognitive score analysed by excluding any tests determined pre-hoc to depend on visual acuity.

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 5000-10000 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 will be analysed as intention to treat (ITT) analysis.

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) from baseline to 36 months between groups using a 2-sample t-test. A secondary analysis involving a linear regression model will be done to estimate the overall three-year change in LASI-DAD global cognitive score from baseline adjusting for potential determinants of change in cognitive status, such as baseline cognitive score, age, sex, education, quality of life, depression, social interaction, and physical activity. Further covariates will be detailed in the SAP. Similar methods will be used for other time-points and secondary outcomes that are continuous data such as INDVFQ, IPAQ, PHQ9 and HMSE scores. Number of falls will be analysed using a two-sample t-test. SNI (categorical data) will be analysed using Chi-square test.

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 and WHO annual mortality rates in the elderly Indian population(ranging between 10.1 % and 12.7 %). Therefore, 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. However, based on available and other local factors as evident from pre-pilot work, 5000-10000 participants may have to be screened for recruiting 760 participants for the trial.

Eligibility criteria: Inclusion Criteria

1. Community dwelling
2. Residency

   a. Participants must plan to reside in the local area for the study duration
3. Presenting vision in the better eye due to uncorrected refractive error

   1. Impaired distance vision less than 6/18
   2. Near vision less than N6 at 40 cm
4. Willingness

   1. to participate
   2. to be randomized
   3. to adhere to the protocol

Exclusion criteria

1. Impaired baseline cognition

   a. HMSE score less than or equal to 18
2. Non-refractive causes of vision impairment
3. Severely impaired mobility

   1. immobile
   2. bedridden
   3. wheelchair
   4. using walker
4. Severe medical illness likely to limit the life span

   1. Cancer
   2. Heart disease
   3. Stroke
   4. HIV or AIDS
   5. Chronic lung disease
   6. Kidney disease
5. Hearing loss assessment

   1. self-reported hearing impairment
   2. inability to hear
   3. fail in whisper test hearing screening(unable to repeat three out of six words)

Primary outcomes:
measure: Change in cognitive score
timeFrame: Time point(s) of primary interest: 36 months collected at 12, 24 and 36 months
Secondary outcomes:
measure: 26-Item Quality of Life
timeFrame: Time point(s) of primary interest: 36 months collected every 12 months - ie at 12, 24 and 36 months
measure: Cost effectiveness
timeFrame: Time point(s) of primary interest: 36 months collected every 12 months - ie at 12, 24 and 36 months
measure: Social interaction/isolation
timeFrame: Time point(s) of primary interest: 36 months collected every 12 months - ie at 12, 24 and 36 months
measure: Self-reported physical activity.
timeFrame: Time point(s) of primary interest: 36 months collected every 12 months - ie at 12, 24 and 36 months
measure: Falls
timeFrame: Time point(s) of primary interest: 36 months collected every 12 months - ie at 12, 24 and 36 months
measure: Depression
timeFrame: Time point(s) of primary interest: 36 months collected every 12 months - ie at 12, 24 and 36 months
measure: Glasses compliance
timeFrame: Time point(s) of primary interest: 36 months collected every 12 months - ie at 12, 24 and 36 months
measure: Visual Function
timeFrame: Time point(s) of primary interest: 36 months collected every 12 months - ie at 12, 24 and 36 months
measure: Domain-specific cognitive function
timeFrame: Time point(s) of primary interest: 36 months collected every 12 months - ie at 12, 24 and 36 months
Other outcomes:
Locations:
city: Hyderabad
country: India
facility: L V Prasad Eye Institute
state: Telangana
Study officials:
affiliation: Queen's University, Belfast
name: Nathan G Congdon, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: L.V. Prasad Eye Institute
name: Rohit C Khanna, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: National Institute of Mental Health and Neuro Sciences, India
name: Suvarna Alladi, DM
role: PRINCIPAL_INVESTIGATOR
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