Neural Correlates of Working Memory Training for HIV Patients

Neural Correlates of Working Memory Training for HIV Patients: A Randomized Control Clinical Trial

Despite potent combination antiretroviral therapy, cognitive (memory and concentration) problems continue to occur in up to 50% of HIV-infected individuals, especially in older infected individuals, and those who abuse alcohol, marijuana or psychostimulants. Since no effective treatments are available to these individuals with cognitive problems, conservative estimates indicate that the cost of care for these patients could double in the next two decades. To address this urgent problem, this study will use a comprehensive approach (cognitive tests, functional MRI and several biomarkers) to evaluate whether a novel computer-based training program would improve the brain function, especially working memory and attention, in HIV-infected and infected individuals.

Study Overview

• Status: Unknown
• Conditions: HIV Infection
• Intervention / Treatment: Other: Adaptive WM CogMed Training; Other: Nonadaptive WM CogMed Training

Detailed Description

The Overall Goals are to perform a double blind placebo-controlled study using Cogmed™ to determine whether this adaptive WM training program will benefit HIV-infected individuals, and whether the investigators can identify individuals who might benefit most from the working memory (WM) training. Lastly, the investigators will explore how brain activation, neuroinflammation and cerebrospinal fluid (CSF) monoamine levels might be related to WM function before and after the training.

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria for HIV-infected participants :

1. Men or women of any ethnicity, ages>18 years and able to provide informed consent,
2. HIV seropositive (with documentation from medical records),
3. Stable on an antiretroviral regimen for 6 months or will remain without antiretroviral treatment during the duration of the study.

Inclusion Criteria for Seronegative (SN) healthy participants :

1. Men or women of any ethnicity, ages > 18 years and able to give informed consent,
2. Seronegative for HIV

Exclusion criteria :

1. Confounding co-morbid psychiatric illness
2. Confounding neurological disorders
3. Abnormal screening laboratory tests (>2 SD) that might indicate a chronic medical condition (e.g. diabetes, severe cardiac, renal or liver disorders)
4. Medications that might influence outcome measures
5. Current or history of drug dependence within the past two years
6. Positive urine toxicology screen
7. Inability to read at an 8th grade level
8. Other contraindications for MR studies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HIV Positive participants; Intervention; 90 HIV positive participants will be trained. Half the participants will have the Adaptive WM Cogmed training, and half will have the non-adaptive WM Cogmed training.	Other: Adaptive WM CogMed Training; 12 different computerized visual and spatial Working Memory tasks will be presented at each sessoin. Each session will involve 8 of the 12 tasks, and each subject is required to complete 25 training sessions, 30-40 minutes per day, 4-5 days per week over a 5-8 week period (minimum 20 sessions). The tasks will become more difficult in an "adaptive" manner, which is hypothesized as optimal for learning and training effects.; Other: Nonadaptive WM CogMed Training; The same 12 computerized visual and spatial working memory tasks will be presented, but at a fixed ("non-adaptive") and low difficulty level. 5 sessions per week x 5 weeks fora total of 25 sessions (minimum 20 sessions).
Other: Seronegative particpiants; Intervention; 90 seronegative participants will be trained. Half the participants will have the Adaptive WM Cogmed training, and half will have the non-adaptive WM Cogmed training.	Other: Adaptive WM CogMed Training; 12 different computerized visual and spatial Working Memory tasks will be presented at each sessoin. Each session will involve 8 of the 12 tasks, and each subject is required to complete 25 training sessions, 30-40 minutes per day, 4-5 days per week over a 5-8 week period (minimum 20 sessions). The tasks will become more difficult in an "adaptive" manner, which is hypothesized as optimal for learning and training effects.; Other: Nonadaptive WM CogMed Training; The same 12 computerized visual and spatial working memory tasks will be presented, but at a fixed ("non-adaptive") and low difficulty level. 5 sessions per week x 5 weeks fora total of 25 sessions (minimum 20 sessions).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the Improvement Index on Cogmed™	This is generated by the computer training program based on the trained tasks.	1 month after training, and 6 month after training completion
Changes in Performances on near transfer working memory tasks	Verbal working memory and spatial working memory tasks	1 month after training, and 6 month after training completion
Changes in Blood-Oxygenation Level-Dependent Functional MRI Measures	Brain activation during the performance of working memory and attention tasks	1 month after training, and 6 month after training completion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in cognitive performance based on LIM homeobox transcription factor 1 alpha (LMX1A) genotypes (AA vs. GA/GG)	Performance and improvements on cognitive tests may vary at baseline and after training based on LMX1A genotypes	Baseline, 1 month after training, and 6 month after training completion
Changes in Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A)	Improvement on BRIEF-A, a self-reported evaluation of the person's executive function during their activities of daily living.	1 month after training, and 6 month after training completion
Changes in Blood-Oxygenation Level-Dependent Functional MRI Measures based on LMX1A genotypes	Brain activation during working memory performance may vary at baseline, 1-month or 6-months based on the different LMX1A genotypes	1 month after training, and 6 month after training completion

Collaborators and Investigators

• Sponsor: University of Hawaii
• Collaborators: National Institute on Drug Abuse (NIDA); University of Maryland, Baltimore
• Investigators: Principal Investigator: Linda Chang, MD, University of Maryland Baltimiore

Publications and helpful links

General Publications

• Chang L, Lohaugen GC, Douet V, Miller EN, Skranes J, Ernst T. Neural correlates of working memory training in HIV patients: study protocol for a randomized controlled trial. Trials. 2016 Feb 2;17:62. doi: 10.1186/s13063-016-1160-4.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2012
• Primary Completion (Anticipated): May 1, 2020
• Study Completion (Anticipated): May 1, 2020

Study Registration Dates

• First Submitted: November 5, 2015
• First Submitted That Met QC Criteria: November 10, 2015
• First Posted (Estimate): November 11, 2015

Study Record Updates

• Last Update Posted (Actual): October 2, 2019
• Last Update Submitted That Met QC Criteria: October 1, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Human Immunodeficiency Virus (HIV); functional magnetic resonance imaging (fMRI); working memory training; brain function
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections
• Other Study ID Numbers: 4R01DA035659-04 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO