Cognitive Function in Patients Treated for Metastatic Melanoma With Immune Checkpoint Inhibitors

Quality of Life Clinical Trial

Official title:

Cognitive Function in Patients Treated for Metastatic Melanoma With Immune Checkpoint Inhibitors: A Controlled Prospective Observational Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04565769
• Other study ID #: 2016-051-000001-1730
• Status: Active, not recruiting
• Start date: November 12, 2020
• Est. completion date: March 2025

Study information

• Verified date: April 2024
• Source: Aarhus University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Immune checkpoint inhibitors (ICIs) are a group of novel immunotherapies that boost the body's own defense against the cancer by improving the immune system's ability to recognize and destroy cancer cells. While it is relatively well-documented that conventional cancer treatments (e.g., chemotherapy) are associated with cognitive impairment, virtually nothing is yet known about effects on cognition during and after ICI treatment. Due to significantly improved survival rates after ICI treatments, it becomes important to map possible adverse effects associated with these treatments. The investigators therefore investigate possible changes in cognitive function in a group of cancer patients from prior to ICI treatment to nine months later. A gender- and age- matched healthy control group will serve as a comparison. The study has the potential to broaden our understanding of associations between cognition, the brain, and the immune system and to provide clinically relevant knowledge about possible cognitive impairments associated with immunotherapy.

Description:

This controlled prospective observational study will include two groups with a total of 84 participants. A total of 42 patients diagnosed with melanoma, referred to treatment with ICI will be enrolled in the study and examined prior to treatment with ICI (baseline), at eight weeks following baseline (T2), at 24 weeks following baseline (T3) and 12 weeks after treatment completed (T4). A total of 42 gender- and age- matched healthy controls will be included and assessed at similar time points. Assessments will include a battery of neuropsychological tests, questionnaires, blood samples, and Magnetic Resonance Imaging (MRI).

The main objectives of the study are to investigate:

1. Changes in cognitive functions over the course of treatment with ICIs.

2. Possible associations between changes in cognitive function and immune markers during and following ICI treatment.

3. Possible associations between changes in cognitive function and changes in brain morphology.

4. Changes over time in other possible adverse effects of ICI treatment, including psychological distress, sleep disturbances, and fatigue.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: March 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Confirmed diagnosis of melanoma and scheduled for ICI treatment at Aarhus University Hospital (AUH), Denmark. The healthy control group will consist of an age- and gender- matched sample of participants.

Exclusion Criteria:

• Previous treatment with immunotherapy

• Neurodegenerative diseases (dementia etc.)

• Substance abuse

• Known progressive psychiatric diseases (e.g., Schizophrenia)

• Other confirmed diagnoses with underlying cognitive impairment

• Insufficient Danish proficiency

Related Conditions & MeSH terms

• Cancer-related Cognitive Impairment
• Cognitive Dysfunction
• Cognitive Impairment
• Depression, Anxiety
• Fatigue
• Illness Behavior
• Inflammation
• Melanoma
• Quality of Life
• Sickness Behavior
• Sleep

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital	Aarhus

Sponsors (2)

Lead Sponsor	Collaborator
Aarhus University Hospital	University of Aarhus

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Attention	Changes in attention as measured with WAIS-IV The Digit Span Forwards (scores with a minimum of 0 points to a maximum of 16 points - higher scores mean a better outcome)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Primary	Attention	Changes in attention as measured with Paced Auditory Serial Addition Test (scores ranging from a minimum of 0 and a maximum of 60 with higher scores indicating a better outcome)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Primary	Processing Speed	Changes in processing speed as measured with WAIS-IV The Digit Symbol coding (scores ranging from a minimum of 0 and a maximum of 135 with higher scores indicating a better outcome)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Primary	Processing Speed	Changes in processing speed as measured with Trail Making Test A (outcome is time in seconds)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Primary	Working memory	Changes in working memory as measured with WAIS-IV The Digit Span Backwards (scores with a minimum of 0 points to a maximum of 16 points - higher scores mean a better outcome)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Primary	Working memory	Changes in working memory as measured with WAIS-IV The Digit Span Ranking (scores with a minimum of 0 points to a maximum of 16 points - higher scores mean a better outcome)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Primary	Learning and memory	Changes in learning and memory as measured with the Hopkins Verbal Learning Test - Revised (part 1 include a minimum score of 0 and a maximum score of 36 with higher score indicating a better outcome, part 2 include a minimum score of 0 and a maximum score of 12 with higher scores indicating better outcomes)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Primary	Learning and memory	Changes in learning and memory as measured with Brief Visuospatial Memory Test - Revised (part 1 include a minimum score of 0 and a maximum score of 18 with a higher score indicating a better outcome, part 2 include a minimum score of 0 and a maximum score of 6 with higher scores indicating better outcomes)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Primary	Visuospatial ability	Changes in visuospatial ability as measured with WAIS-IV Matrix Reasoning (scores with a minimum of 0 and a maximum of 26 with higher scores indicating better outcomes)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Primary	Verbal fluency	Changes in verbal fluency as measured with the Controlled Oral Word Association Test, letter and animal (as many words as possible, more words indicating a better outcome. No maximum value)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Primary	Executive function	Changes in executive function as measured with the Trail Making Test B (outcome is time in seconds)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Secondary	Cancer-related fatigue	Changes in fatigue severity as measured with The Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT fatigue) scale (range from 0 to 52. Items are reverse scored when appropriate to provide a scale in which higher scores represent better functioning or less fatigue)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Secondary	Sleep quality	Changes in sleep quality as measured with the Insomnia Severity Index (ISI) (scores ranging from a minimum of 0 and a maximum of 28 with higher scores indicating higher levels of insomnia)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Secondary	Sleep quality	Changes in sleep quality as measured with the Pittsburgh Sleep Quality Index (PSQI) (scores ranging form a minimum of 0 indicating no difficulty and a maximum of 21 indicating severe difficulties in all areas related to sleep)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Secondary	Perceived cognitive functioning	Changes in perceived cognitive functioning as measured with The Patient Assessment of Own Functioning Inventory (PAOFI) (outcome is scores ranging from a minimum of 35 to a maximum of 210)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Secondary	Depression/Anxiety	Changes in depression/anxiety as measured with the Hospital Anxiety and Depression Scale (HADS) (range from a minimum score of 0 to a maximum score of 21 in which a higher scores mean higher levels of depression/anxiety)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Secondary	Sickness behavior	Changes in subjective sickness behavior as measured with the Sickness Questionnaire (SicknessQ) (scores ranging from a minimum of 0 and a maximum of 30 with higher scores indicating worse outcome)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Secondary	Health-related quality of life	Changes in health-related quality of life as measured with The European Organization for Research and Treatment of Cancer, Quality of Life questionnaire for cancer patients (EORTC QLQ-C30) (all of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.)	Baseline, and week 8, 24 and 12 weeks after completed treatment
Secondary	Moderator: genotype	Genotype of COMT and APOE4; Genotype of COMT	Baseline
Secondary	Inflammatory immune markers	TNF-a, IL-6, IL-8, IL-21, CRP, IP-10 and MCP-1 extracted from blood samples	Baseline, and week 8, 24 and 12 weeks after completed treatment
Secondary	Brain grey matter	Changes in brain grey matter as measured with T1-weighted MRI	Baseline and week 24.
Secondary	Brain white matter	Changes in brain white matter as measured with T1-weighted MRI	Baseline and week 24.