Cognitive Biomarker Development for Chronic Conditions

Overseen By MATTHEW D Maple

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Minnesota

Disqualifiers: Under 18, Non-English speaking, Pregnant

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 1-7 days

45 Participants Needed

Trial Summary

What is the purpose of this trial?

The overall objective of this study is to determine the feasibility of identifying transdiagnostic biomarkers of cognitive function mediated by neuromodulation of the dorsolateral prefrontal cortex that are translatable across disease groups in order to more accurately phenotype clusters of cognitive dysfunction. Completing behavioral paradigms with electrophysiology and TMS is a challenging frontier. This study focuses on the feasibility of such an endeavor for those with chronic pain or depression as well as healthy controls.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators.

What data supports the effectiveness of the treatment Transdiagnostic Cognitive Biomarkers for chronic conditions?

Research shows that many chronic diseases, like diabetes and heart failure, are linked to cognitive symptoms, and treatments often improve cognitive functioning without adverse effects. Additionally, mobile cognitive assessments have shown promise in tracking cognitive changes, suggesting that cognitive-focused treatments could be beneficial. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

Research shows that many medical treatments, including those for chronic conditions, often do not have adverse effects on cognitive functions, and some may even improve them. However, it's important to monitor for potential cognitive side effects, especially when multiple medications are used together, as they can sometimes lead to cognitive impairment. ^{2 6 7 8 9}

How does this treatment differ from other treatments for chronic conditions?

This treatment is unique because it focuses on developing cognitive biomarkers, which are indicators of cognitive function, to better understand and manage chronic conditions. Unlike traditional treatments that may focus solely on physical symptoms, this approach aims to assess and improve cognitive health, potentially leading to more comprehensive care. ^{2 4 10 11 12}

Eligibility Criteria

This trial is for adults who can access the online study platform and are experiencing chronic pain or depression. It's not suitable for individuals under 18, those who don't speak English, or pregnant women.

Inclusion Criteria

Have access to the online study platform.

I am experiencing pain or depression.

Exclusion Criteria

You are pregnant.

I am under 18 years old and do not speak English.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants undergo MRI, TMS, EEG, and complete behavioral tasks and surveys

1-7 days

Multiple visits (in-person and online)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Transdiagnostic Cognitive Biomarkers

Trial Overview The study is testing if playing computer games/tasks and completing health surveys online can help identify cognitive biomarkers across different conditions like pain and depression.

Participant Groups

Group I: Pain/Depression patients from clinic Experimental Treatment 2 Interventions

MRI, TMS and EEG, and behavioral tasks and surveys online.

Group II: Healthy Comparison Group Active Control 2 Interventions

Behavioral tasks and surveys online.

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Findings from Research

Patients newly diagnosed with schizophrenia showed significant impairments in attention and processing speed, which were linked to their rates of hospitalization and outpatient care, indicating that cognitive function plays a role in clinical outcomes.

The length of hospitalization was primarily influenced by the subtype of schizophrenia, suggesting that the type of diagnosis is more critical than cognitive function in determining treatment duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prediction of patient contacts by cognition in schizophrenia. Ernst Nielsen, R., Haugaard, C., Olrik Wallenstein Jensen, S., et al.[2013]

A review of various medical treatments across different patient populations shows that cognitive evaluations in clinical trials often reveal either no negative cognitive effects or even improvements in cognitive functioning after treatment.

Despite the positive findings, there are significant challenges in consistently measuring cognitive changes over time and determining what constitutes clinically meaningful impairment, which need to be addressed before cognitive assessments can be standard in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the effects of treatment for medical disorders: has the value of neuropsychological assessment been fully realized? Ryan, CM., Hendrickson, R.[2014]

A review of 32 studies on self-reported cognitive symptoms in nonneurological chronic conditions revealed a wide variety of assessment tools, with 28 different instruments used, highlighting the need for standardization in measuring cognitive function.

Most studies found that self-reported cognitive symptoms were not consistently correlated with neuropsychological test results, but there was a strong association between self-reported cognitive function and other patient-reported outcomes, suggesting that subjective experiences of cognitive issues are important in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Self-Reported Cognitive Function in Persons with Nonneurological Chronic Diseases: A Systematic Review. Cuevas, H., Danesh, V., Henneghan, A.[2022]

Mobile cognitive assessments conducted via smartphones show promise as a complementary tool to traditional methods, with studies indicating high adherence rates of 79.2% and strong reliability and validity in measuring cognitive function.

These assessments, which sampled participants frequently over short periods, can help detect subtle cognitive declines in everyday settings, making them valuable for patient-centered care and ongoing monitoring of cognitive health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Applications for self-administered mobile cognitive assessments in clinical research: A systematic review. Moore, RC., Swendsen, J., Depp, CA.[2022]

In a study of 692 older adults, a strong inverse relationship was found between medical burden (the number of chronic conditions) and cognitive performance, indicating that more medical issues lead to worse cognitive function.

Specifically, individuals with five or more chronic conditions showed significant deficits in attention, particularly in tasks requiring quick and divided attention, which may impact their ability to follow medical advice and achieve better health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medical burden and cognition in older patients in primary care: selective deficits in attention. Duff, K., Mold, JW., Roberts, MM., et al.[2007]

The study emphasizes the importance of including cognitive function assessments in safety pharmacology for drugs that affect the central nervous system, as cognitive deficits can be a significant side effect.

Using various tests on rodents, such as the passive avoidance and Morris water maze tests, the research demonstrated that standard drugs like diazepam and scopolamine can reliably induce cognitive impairments, highlighting the potential for these assays to evaluate the cognitive safety of new CNS drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CNS safety pharmacology: A focus on cognitive functions. Hernier, AM., Froger-Colléaux, C., Castagné, V.[2019]

From 1999 to 2016, the use of medications with cognitive side effects among adults aged 60 and older increased significantly, with a staggering 298.7% rise in those taking three or more such medications.

Older adults using three or more medications with cognitive side effects scored lower on cognitive tests, indicating a link between polypharmacy and cognitive impairment, which underscores the importance of cognitive screenings for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utilization of Medications With Cognitive Impairment Side Effects and the Implications for Older Adults' Cognitive Function. Do, D., Schnittker, J.[2021]

In a study of 7728 nursing home residents with Alzheimer's disease and psychosis, the most common adverse event was accidental injury, occurring at a rate of 97.7 per 100 person-years, highlighting the vulnerability of this population.

Other significant adverse events included death (44.6 per 100 person-years), infection (41.8 per 100 person-years), and pain (43.5 per 100 person-years), indicating a high incidence of serious health issues among these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events among nursing home residents with Alzheimer's disease and psychosis. Oliveria, SA., Liperoti, R., L'italien, G., et al.[2019]

A new individualized method for detecting cognitive adverse events (CAEs) in patients with advanced dementia undergoing electroconvulsive therapy (ECT) was developed, focusing on specific cognitive measures and functional scales.

The monitoring plan defines CAEs based on specific score declines: a ≥6 point drop on the Severe Impairment Battery-8 for patients without floor effects, and a ≥30 point drop on the Barthel Index for those with floor effects, ensuring accurate detection of cognitive changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Approach to Monitoring Cognitive Adverse Events for Interventional Studies Involving Advanced Dementia Patients: Insights From the Electroconvulsive Therapy for Agitation in Dementia Study. Park, S., Forester, BP., Lapid, MI., et al.[2023]

The clock drawing test was validated as a simple and effective method for assessing cognitive function in a study of 138 elderly individuals, showing a strong correlation (0.73) with the Mini Mental State test.

With a cutoff score of 7 points on the clock drawing test, it demonstrated a sensitivity of 0.82 and specificity of 0.71 for diagnosing dementia, indicating its potential usefulness in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The clock test: a simple method to assess dementia]. García, CE., Loyola, JC., Armstrong, T., et al.[2022]

The upgraded experience-sampling tool for assessing momentary cognition tasks was found to be feasible, with a high completion rate of 71% among 49 healthy adults, indicating that participants were motivated and engaged with the tasks.

The momentary Digit Symbol Substitution Task (mDSST) was identified as the most sensitive measure for capturing cognitive performance variability, while the momentary Visuospatial Working Memory Task (mVSWMT) proved too challenging, suggesting the need for adjustments to improve its validity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Digital assessment of working memory and processing speed in everyday life: Feasibility, validation, and lessons-learned. Daniëls, NEM., Bartels, SL., Verhagen, SJW., et al.[2022]

The Test of Everyday Attention (TEA) was developed from a study involving 154 participants and effectively measures various types of attention, including sustained attention and selective attention, correlating well with existing attention measures.

TEA demonstrates high reliability and can distinguish between different brain-impaired groups, making it a valuable tool for assessing attention in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The structure of normal human attention: The Test of Everyday Attention. Robertson, IH., Ward, T., Ridgeway, V., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Prediction of patient contacts by cognition in schizophrenia. [2013]

2. United States pubmed.ncbi.nlm.nih.gov

Evaluating the effects of treatment for medical disorders: has the value of neuropsychological assessment been fully realized? [2014]

3. United States pubmed.ncbi.nlm.nih.gov

Self-Reported Cognitive Function in Persons with Nonneurological Chronic Diseases: A Systematic Review. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Applications for self-administered mobile cognitive assessments in clinical research: A systematic review. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Medical burden and cognition in older patients in primary care: selective deficits in attention. [2007]

6. United States pubmed.ncbi.nlm.nih.gov

CNS safety pharmacology: A focus on cognitive functions. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Utilization of Medications With Cognitive Impairment Side Effects and the Implications for Older Adults' Cognitive Function. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Adverse events among nursing home residents with Alzheimer's disease and psychosis. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

A Novel Approach to Monitoring Cognitive Adverse Events for Interventional Studies Involving Advanced Dementia Patients: Insights From the Electroconvulsive Therapy for Agitation in Dementia Study. [2023]

10. Chile pubmed.ncbi.nlm.nih.gov

[The clock test: a simple method to assess dementia]. [2022]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Digital assessment of working memory and processing speed in everyday life: Feasibility, validation, and lessons-learned. [2022]

12. England pubmed.ncbi.nlm.nih.gov

The structure of normal human attention: The Test of Everyday Attention. [2022]