Teleneuropsychological Intervention in Asymptomatic HIV Seropositive Patients: N&C NeuroChange

Study Overview
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Brief Summary
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Currently 37.9 million people are living with human immunodeficiency virus (HIV) around the world (UNAIDS, 2018). Even with antiretroviral treatment (ART), the virus enters the central nervous system and can affect the following structures: amygdala, hippocampus, thalamus, parietal, frontal, temporal regions, orbitofrontal, cingulate, motor and sensory cortex; generating cognitive, behavioral and motor alterations, up to HIV-associated neurocognitive disorder (HAND) and occasionally HIV-associated dementia (HAD). Few clinical studies have been conducted using computerized cognitive rehabilitation programs to counteract neuropsychological alterations. The aim of this project is to explore the feasibility of a cognitive stimulation program (CSP) developed to strengthen cognitive domains identified as impaired through a neuropsychological assessment in asymptomatic HIV+ patients adherent to ART, with the purpose of improving their quality of life and mood disorder.

Detailed Description
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A pilot randomized controlled trial (RCT) will be conducted with a study group and a control group in waiting list. This design will be used because it allows to evaluate the feasibility of a teleneuropsychological intervention (N&C NeuroChange) and to identify a preliminary effect as a first approach in a given population, provides greater experimental control over the study variables and allows pre-intervention, post-intervention and follow-up comparisons. Lancaster et al. (2004) state that n=30 is acceptable for a pilot study, while (Julious, 2005) suggest a minimum sample of n=12 per group. Therefore, 24 participants will be recruited for this study. This has already been implemented in other pilot studies that sought to identify the efficacy of an intervention using samples of 20 (Berrymam et al., 2020) and 13 participants (Delaney, 2018) in total. Although the size of the sample may be a methodological limitation, it will be considered in the discussion of the results; in addition to being a preliminary study to carry out a more rigorous study with an RCT. Participants will be eligible if they are between 20 and 45 years old because 77.5% of the reported cases are in this age range in Mexico (CENSIDA, 2022) . The procedure will be as follows: All participants will be explained what the study consists of, the intervention and will be given informed consent. Patients will be recruited from the Specialized Clinic Condesa Iztapalapa that serves people living with HIV. A brief medical history will begin with an interview to collect medical history (HIV pathological and infectious history such as time of evolution, viral load, CD4 level, ART regimen, as well as substance abuse and cognitive complaints) and then a neuropsychological assessment will be performed. With those candidates who meet the inclusion criteria and wish to participate, will be randomly assigned in a 1:1 ratio to the intervention group or waiting list control arm. The intervention will begin first with the study group, and a subsequent evaluation will be carried out and then the intervention will be applied to the control group on the waiting list, which will also undergo a subsequent evaluation. Both groups will undergo a third follow-up evaluation three months later to identify whether the changes were maintained over time. Main outcomes of interest include evaluation of the achievement of intervention objectives, usability and acceptability of the CSP. Baseline and follow up measures include assessment of attention, memory, visuospatial skills, working memory, processing speed, verbal fluency, planning, abstraction, depressive and anxiety symptomatology, and daily functionality.

Official Title
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Feasibility and Usefulness of a Neuropsychological Telerehabilitation Program in Asymptomatic HIV Patients: Pilot Randomized Controlled Trial

Conditions
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Telerehabilitation, Neuropsychology, HIV Dementia

Intervention / Treatment
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* Behavioral: Cognitive stimulation program


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or females with HIV Minimum primary education From 20 to 45 years old Normal or corrected vision and hearing Treatment adherence Exclusion Criteria: Neurological and psychiatric history (except mood disorders) Head injuries Cerebrovascular events Substance abuse AIDS associated diseases Hormonal therapy

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A pilot randomized clinical trial will be conducted with HIV+ participants randomised in a 1:1 ratio to a study group that will receive the neuropsychological intervention and a second control group that will remain waiting until the study group finishes the intervention and after that can receive the intervention.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study group<br>Refers to the experimental group that will receive the cognitive stimulation program intervention. | Behavioral: Cognitive stimulation program<br>* The cognitive stimulation program consists of 12 sessions of approximately 45 minutes, distributed in a first stage of training and psychoeducation (1 session), a second stage to address emotional aspects of anxiety and depression (2 sessions), and neuropsychological training (8 sessions) and a final closing stage with one session. There will be two sessions per week for 6 weeks. The neuropsychological training includes 20 activities whose level of difficulty will vary according to the number of stimuli and the time of stimuli presentation. It includes 5 attentional activities, 3 memory activities, 5 executive functioning activities, one visuospatial skills activity and 6 ecological activities. These activities will be developed on a digital computer platform where patients will be assigned an identification and password to ensure confidentiality.<br>* Other names: N&C NeuroChange;|
| Other: Waiting list control group<br>Will be the control group that remains without intervention until the study group completes the cognitive stimulation program and the subsequent neuropsychological assessment has been done. Once the intervention is completed with the study group, the same program will be applied to the control group. | Behavioral: Cognitive stimulation program<br>* The cognitive stimulation program consists of 12 sessions of approximately 45 minutes, distributed in a first stage of training and psychoeducation (1 session), a second stage to address emotional aspects of anxiety and depression (2 sessions), and neuropsychological training (8 sessions) and a final closing stage with one session. There will be two sessions per week for 6 weeks. The neuropsychological training includes 20 activities whose level of difficulty will vary according to the number of stimuli and the time of stimuli presentation. It includes 5 attentional activities, 3 memory activities, 5 executive functioning activities, one visuospatial skills activity and 6 ecological activities. These activities will be developed on a digital computer platform where patients will be assigned an identification and password to ensure confidentiality.<br>* Other names: N&C NeuroChange;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Attention | Direct digits of the Integrated Neuropsychological Exploration Program. The repetition of a series of digits is requested and an element is added as the task progresses. Uses percentile scores. | Baseline | 
| Memory | Immediate and deferred texts, and word learning of the Integrated Neuropsychological Exploration Program. Two stories are read and at the end of each one, the patient is asked to narrate everything he/she remembers from the story. In case of not remembering elements, questions are asked about the missing information. The stories are asked again after 5 minutes. Uses percentile scores. | Baseline | 
| Visuospatial skills | Rey Figure of the NEUROPSI A&M. A complex figure is copied from a model. Afterwards, the figure is drawn again without the model. Uses scalar scores. | Baseline | 
| Working memory | Digits and letters of the Weschler Adults Intelligence Scale IV. Numbers and letters are provided in disorder and all the elements are asked to be repeated in order, first the numbers and then the letters. Uses scalar scores. | Baseline | 
| Processing speed | Word reading of Stroop test. A list of 5 columns of words with 20 items each is read as quickly as possible. Uses percentile scores. | Baseline | 
| Verbal fluency | Categorical recall of the Integrated Neuropsychological Exploration Program. The highest number of animals is said in one minute and the highest number of words beginning with p in three minutes. Uses percentile scores. | Baseline | 
| Planning | Zoo test of the Behavioral Assessment of Dysexecutive Syndrome and Behavioral Rating Inventory of Executive Functioning for Adults. Consists in marking a route in a zoo map to visit different places. Afterwards, the person marks again in the zoo map a rout but is told which route to follow. | Baseline | 
| Abstraction | Resemblances of the Weschler Adults Intelligence Scale IV. Consists in mentioning what two words have in common or how they are similar. Uses scalar scores. | Baseline | 
| Attention | Direct digits of the Integrated Neuropsychological Exploration Program. The repetition of a series of digits is requested and an element is added as the task progresses. Uses percentile scores. | Immediately after the intervention | 
| Memory | Immediate and deferred texts, and word learning of the Integrated Neuropsychological Exploration Program. Two stories are read and at the end of each one, the patient is asked to narrate everything he/she remembers from the story. In case of not remembering elements, questions are asked about the missing information. The stories are asked again after 5 minutes. Uses percentile scores. | Immediately after the intervention | 
| Visuospatial skills | Rey Figure of the NEUROPSI A&M. A complex figure is copied from a model. Afterwards, the figure is drawn again without the model. Uses scalar scores. | Immediately after the intervention | 
| Working memory | Digits and letters of the Weschler Adults Intelligence Scale IV. Numbers and letters are provided in disorder and all the elements are asked to be repeated in order, first the numbers and then the letters. Uses scalar scores. | Immediately after the intervention | 
| Processing speed | Word reading of Stroop test. A list of 5 columns of words with 20 items each is read as quickly as possible. Uses percentile scores. | Immediately after the intervention | 
| Verbal fluency | Categorical recall of the Integrated Neuropsychological Exploration Program. The highest number of animals is said in one minute and the highest number of words beginning with p in three minutes. Uses percentile scores. | Immediately after the intervention | 
| Planning | Zoo test of the Behavioral Assessment of Dysexecutive Syndrome and Behavioral Rating Inventory of Executive Functioning for Adults. Consists in marking a route in a zoo map to visit different places. Afterwards, the person marks again in the zoo map a rout but is told which route to follow. | Immediately after the intervention | 
| Abstraction | Resemblances of the Weschler Adults Intelligence Scale IV. Consists in mentioning what two words have in common or how they are similar. Uses scalar scores. | Immediately after the intervention | 
| Attention | Direct digits of the Integrated Neuropsychological Exploration Program. The repetition of a series of digits is requested and an element is added as the task progresses. Uses percentile scores. | Up to 12 weeks | 
| Memory | Immediate and deferred texts, and word learning of the Integrated Neuropsychological Exploration Program. Two stories are read and at the end of each one, the patient is asked to narrate everything he/she remembers from the story. In case of not remembering elements, questions are asked about the missing information. The stories are asked again after 5 minutes. Uses percentile scores. | Up to 12 weeks | 
| Visuospatial skills | Rey Figure of the NEUROPSI A&M. A complex figure is copied from a model. Afterwards, the figure is drawn again without the model. Uses scalar scores. | Up to 12 weeks | 
| Working memory | Digits and letters of the Weschler Adults Intelligence Scale IV. Numbers and letters are provided in disorder and all the elements are asked to be repeated in order, first the numbers and then the letters. Uses scalar scores. | Up to 12 weeks | 
| Processing speed | Word reading of Stroop test. A list of 5 columns of words with 20 items each is read as quickly as possible. Uses percentile scores. | Up to 12 weeks | 
| Verbal fluency | Categorical recall of the Integrated Neuropsychological Exploration Program. The highest number of animals is said in one minute and the highest number of words beginning with p in three minutes. Uses percentile scores. | Up to 12 weeks | 
| Planning | Zoo test of the Behavioral Assessment of Dysexecutive Syndrome and Behavioral Rating Inventory of Executive Functioning for Adults. Consists in marking a route in a zoo map to visit different places. Afterwards, the person marks again in the zoo map a rout but is told which route to follow. | Up to 12 weeks | 
| Abstraction | Resemblances of the Weschler Adults Intelligence Scale IV. Consists in mentioning what two words have in common or how they are similar. Uses scalar scores. | Up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depressive Symptoms | Patient Health Questionnaire - 9. A self-applied questionnaire that identifies the presence of depressive symptomatology based on a Likert-type scale of 9 items. Based on the cut-off points, minimal (0-4), mild (5-9), moderate (10-14), moderate to severe (15-19) and severe (20-27) depression can be identified. | Baseline | 
| Anxiety symptoms | General Anxiety Disorder - 7. A self-applied scale to identify generalized anxiety. It consists of a self-applied questionnaire of seven Likert-type questions. Based on the cut-off points, no anxiety (0-4), mild anxiety symptoms (5-9), moderate anxiety symptoms (10-14) and severe anxiety symptoms (15-21) can be identified. | Baseline | 
| Daily functionality | The Activities of Daily Living Questionnaire. This instrument evaluates daily functioning by assessing basic and instrumental activities in six areas (self-care, home activities, work, recreation, money management, travel and communication, and information technology); it is usually useful for patients with mild cognitive or motor limitations. It allows to generate a percentage of functional impairment by adding the scores of each item among the total number of responses per 100. | Baseline | 
| Depressive Symptoms | Patient Health Questionnaire - 9. A self-applied questionnaire that identifies the presence of depressive symptomatology based on a Likert-type scale of 9 items. Based on the cut-off points, minimal (0-4), mild (5-9), moderate (10-14), moderate to severe (15-19) and severe (20-27) depression can be identified. | Immediately after the intervention | 
| Anxiety symptoms | General Anxiety Disorder - 7. A self-applied scale to identify generalized anxiety. It consists of a self-applied questionnaire of seven Likert-type questions. Based on the cut-off points, no anxiety (0-4), mild anxiety symptoms (5-9), moderate anxiety symptoms (10-14) and severe anxiety symptoms (15-21) can be identified. | Immediately after the intervention | 
| Daily functionality | The Activities of Daily Living Questionnaire. This instrument evaluates daily functioning by assessing basic and instrumental activities in six areas (self-care, home activities, work, recreation, money management, travel and communication, and information technology); it is usually useful for patients with mild cognitive or motor limitations. It allows to generate a percentage of functional impairment by adding the scores of each item among the total number of responses per 100. | Immediately after the intervention | 
| Depressive Symptoms | Patient Health Questionnaire - 9. A self-applied questionnaire that identifies the presence of depressive symptomatology based on a Likert-type scale of 9 items. Based on the cut-off points, minimal (0-4), mild (5-9), moderate (10-14), moderate to severe (15-19) and severe (20-27) depression can be identified. | Up to 12 weeks | 
| Anxiety symptoms | General Anxiety Disorder - 7. A self-applied scale to identify generalized anxiety. It consists of a self-applied questionnaire of seven Likert-type questions. Based on the cut-off points, no anxiety (0-4), mild anxiety symptoms (5-9), moderate anxiety symptoms (10-14) and severe anxiety symptoms (15-21) can be identified. | Up to 12 weeks | 
| Daily functionality | The Activities of Daily Living Questionnaire. This instrument evaluates daily functioning by assessing basic and instrumental activities in six areas (self-care, home activities, work, recreation, money management, travel and communication, and information technology); it is usually useful for patients with mild cognitive or motor limitations. It allows to generate a percentage of functional impairment by adding the scores of each item among the total number of responses per 100. | Up to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, HAND, Teleneuropsychological intervention