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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks new ways to measure brain function in individuals with chronic pain or depression. Researchers are testing whether tools like brain scans and mental tasks can identify common patterns in brain activity across these conditions. Participants with chronic pain or depression, along with healthy individuals, will help determine the effectiveness of these new measures, known as Transdiagnostic Cognitive Biomarkers. Those experiencing chronic pain or depression and interested in the relationship between brain function and these conditions might be suitable candidates. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new insights and treatments.

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 prior data suggests that this method is safe for participants?

Research has shown that treatments focusing on shared brain patterns in conditions like anxiety and depression are generally safe. These treatments examine common brain activity across different conditions. Previous studies have investigated brain activity and connections related to these conditions without major safety concerns.

For treatments using tools like MRI, TMS (which uses magnetic fields to stimulate nerve cells), and EEG (which measures electrical activity in the brain), safety is well-documented. Researchers commonly use these methods, and participants generally tolerate them well. Most people experience little to no side effects, although some might feel mild discomfort or a headache, especially with TMS.

Overall, evidence suggests that these procedures are safe for people with chronic pain or depression and for healthy volunteers. Participants should always discuss personal concerns with the study team. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the development of transdiagnostic cognitive biomarkers for chronic conditions like pain and depression because these biomarkers offer a new way to understand and assess these conditions beyond traditional methods. Unlike standard treatments that focus on symptom management, such as medications or therapy, these biomarkers aim to identify underlying cognitive patterns using tools like MRI, TMS, and EEG. This approach could lead to more personalized treatment plans by identifying specific cognitive markers associated with each patient's experience of pain or depression. By advancing our understanding of the cognitive aspects of these conditions, researchers hope to create more targeted and effective treatments in the future.

What evidence suggests that this trial's treatments could be effective for cognitive dysfunction in chronic pain or depression?

Research has shown that certain brain patterns, called cognitive biomarkers, can aid in understanding and treating chronic pain and depression. These biomarkers reveal patterns of anxiety and depression that often accompany chronic pain. For instance, one study found that altering emotional perspectives helped individuals with chronic pain and anxiety feel better. Another study suggested that specific brain connections might predict treatment response. Although this research is ongoing, early findings suggest that identifying these biomarkers could improve treatment outcomes for individuals with chronic pain and depression. Participants in this trial will be divided into two groups: one consisting of pain and depression patients from a clinic, and a healthy comparison group. The trial will use MRI, TMS, EEG, and behavioral tasks and surveys to study these biomarkers. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04864080?tab=table

NCT04864080 | Transdiagnostic Cognitive Biomarkers This study aims to test the feasibility of procedures aimed at discovering transdiagnostic biomarkers for cognitive impairment in chronic pain and depression.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8135031/

Initial Outcomes of Transdiagnostic Internet-Delivered ... Primary outcomes included changes in depression, anxiety, and PTSD symptoms. Secondary outcomes included changes in functional impairment; symptoms of panic, ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8832108/

Transdiagnostic Cognitive Processes in Chronic Pain and ... Ruminative absorption on pain is a cognitive process that transverses diagnoses and contributes to worse outcomes.

4. journals.lww.com journals.lww.com/pain/fulltext/2019/08000/efficacy_of_a_transdiagnostic_emotion_focused.6.aspx

Efficacy of a transdiagnostic emotion–focused exposure... Efficacy of a transdiagnostic emotion–focused exposure treatment for chronic pain patients with comorbid anxiety and depression: a randomized controlled trial.

5. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2838443

Predicting Transdiagnostic Treatment Outcomes in ... This prognostic study uses predictive modeling to investigate whether pretreatment whole-brain functional connectivity patterns can be used ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8474161/

Transdiagnostic biomarker approaches to mental health ... Transdiagnostic features of anxiety, depression and anhedonia have been examined in relation to brain activity and connectivity patterns.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12467211/

Mapping the Neuroimmune Web of Pain, Mood, and Memory Mounting evidence situates mood disturbance, memory decline, and chronic pain within a single neuro-immune conversation [1,2].

8. sciencedirect.com sciencedirect.com/science/article/pii/S0149763423004001

Transdiagnostic biomarkers of mental illness across the ... This systematic review synthesizes evidence from research investigating the biological correlates of latent transdiagnostic dimensions of psychopathology.

9. nature.com nature.com/articles/s41746-025-01860-3

Transdiagnostic-focused apps for depression and anxiety This meta-analysis evaluated the efficacy of transdiagnostic-focused apps for depression and anxiety, and aimed to understand how they compare to diagnostic- ...