A Pilot Randomized Controlled Trial: CoINTEGRATE (CoINTEGRATE)

A Pilot Randomized Controlled Trial of A Comprehensive Cognitive and Affective Intervention for Neurocognitive Disorders (CoINTEGRATE)

The purpose of this study is to examine the feasibility of comprehensive multimodal individually tailored Cognitive Behavioral Therapy (CBT), Cognitive Rehabilitation Therapy (CRT), and modifiable lifestyle sessions.

The study team hypothesizes that combining evidence-based cognitive and affective therapies with lifestyle modifications is feasible and will improve the community integration (CI) and Quality of life (QoL) in patients with a neurocognitive disorder compared to usual care.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis; Neurocognitive Disorders; Cognitive Dysfunction; Traumatic Brain Injury; Mild Cognitive Impairment
• Intervention / Treatment: Behavioral: CRT; Behavioral: CBT; Behavioral: Modifiable lifestyle factors; Behavioral: Usual care Psychoeducation

• Study Type: Interventional
• Enrollment (Estimated): 56
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Zee Petrie; Phone Number: 734-647-3357; Email: petrieli@med.umich.edu
• Study Contact Backup: Name: Hala Darwish, PhD; Phone Number: 734-647-4929; Email: darwishh@med.umich.edu

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
      • Contact: Zee Petrie; Phone Number: 734-647-3357; Email: petrieli@med.umich.edu
      • Principal Investigator: Hala Darwish, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosed with one of the following: Mild Trauma Brain injury (TBI), Multiple Sclerosis (MS), Long COVID, or Mild Cognitive Impairment (MCI)
• MCI patients age older than 50 years old, all other diagnosis 21-65 years old and are receiving care through the Michigan medicine network
• Participants that can provide consent or legally authorized representative who can provide consent on their behalf
• Cognitive impairment ≥ 1.0 standard deviation below the test score normed for age and education in at least 2 cognitive domains (verbal learning and memory, processing speed, or visuospatial memory)

Exclusion Criteria:

• TBI participants symptomatic at rest (headache, dizziness, nausea, or vertigo) will be referred to primary care physician (PCP)
• History of TBI (except for participants with TBI)
• MS participants with recent relapse (1 month prior to enrollment) or on Intravenous or oral steroids
• MCI participants with disease duration greater than 1 year
• Patients with other neurosensory or neurodegenerative diseases
• Diagnosed with COVID-19 (except for Long COVID group)
• Psychiatric disorders other than mild to moderate anxiety and depression
• Patients with severe depression or suicidal (ideation or plan) will be instructed to seek mental health, provided with resources and referred to patient's primary care provider
• Diagnosed sleep disorders
• Visual or auditory impairment,
• Current or history of alcohol or substance abuse/dependence
• Cognitive impairment less than 1.0 standard deviation below the test score normed for age and education in at least 2 cognitive domains (verbal learning and memory, processing speed, or visuospatial memory)
• Cognitive impairment greater or equal to 1.0 standard deviation below the test score normed for age and education in 1 cognitive domain (verbal learning and memory, processing speed, or visuospatial memory)
• Currently receiving CRT, CBT or Occupational therapy (OT) or another type of psychological therapy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Usual care	Behavioral: Usual care Psychoeducation; Participants will receive 15 minute psychoeducation session twice per week for 8 weeks. All research-related sessions will be web-based (on Zoom) and recorded (with approval).
Experimental: CRT plus CBT and Lifestyle modifications	Behavioral: CRT; Participants that score 1-1.5 standard deviation (SD) below the norm for age and education on 2 cognitive domains will receive an intensive program, 2 CRT sessions per week for 4 weeks in addition to 1 CBT session per week for 8 weeks. Based on clinical experience, those with more severe cognitive deficits require more time to achieve their therapy goals, whereas those with mild deficits can tolerate a more intense therapy. Participants that score 1.5-2 SD or more below the norm for age and education on 2 cognitive domains will receive 1 CRT and 1 CBT weekly sessions for 8 weeks. All the CRT sessions will be coupled with homework for 8 weeks. All research-related sessions will be web-based (on Zoom) and recorded (with approval).; Behavioral: CBT; Participants that score 1-1.5 standard deviation (SD) below the norm for age and education on 2 cognitive domains will receive an intensive program, 2 CRT sessions per week for 4 weeks in addition to 1 CBT session per week for 8 weeks. Based on clinical experience, those with more severe cognitive deficits require more time to achieve their therapy goals, whereas those with mild deficits can tolerate a more intense therapy. Participants that score 1.5-2 SD or more below the norm for age and education on 2 cognitive domains will receive 1 CRT and 1 CBT weekly sessions for 8 weeks. All the CRT sessions will be coupled with homework for 8 weeks. All research-related sessions will be web-based (on Zoom) and recorded (with approval).; Behavioral: Modifiable lifestyle factors; The therapy sessions are coupled with homework and requires some lifestyle modifications such lifestyle adjustments are using a calendar, a diary, maintaining a sleep schedule and exercise.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients that complete the study		week 8 (end of treatment)
Average number of sessions completed		week 8 (end of treatment)
Overall experience based qualitative semi-structured interview	This interview will be conducted at the end of the study and in the order of exit of participants to gather feedback about their satisfaction with the study. This brief interview consists of 3 questions that ask the participants to describe the aspects of the intervention participants found beneficial, willingness to participate again, and whether it was appropriate for participants needs. In addition, a brief quantitative satisfaction survey to rate overall satisfaction, how likely it would be recommend to others, and how satisfied participants are with telemedicine as a mode of delivery.	Week 9 (after treatment ended)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Community Integration Questionnaire (CIQ) Score	This questionnaire contains 15 items to evaluate the degree of integration into each of the three area of home, social network, and productive activities. The overall score, which represents a summation of the home integration score plus social integration score plus productivity score, can range from 0 to 29. A high score indicates greater integration, and a low score reflects less integration.	Week 9 (after treatment ended)
The Short Form Health Survey (SF-36)	The SF-36 explores people's physical and mental health. It consists of 36 items that assess role limitations due to personal or emotional problems, emotional well-being, social functioning, general health perceptions, perceived change in health. Scores ranged from 0 (worst health status) to 100 (best health status).	Week 9 (after treatment ended)
Montreal Cognitive Assessment (MoCA)	The Montreal Cognitive Assessment (MoCA) was designed as a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. Time to administer the MoCA is approximately 10 minutes. The total possible score is 30 points; a score of 26 or above is considered normal.	Week 9 (after treatment ended)
The Symbol Digit Modalities Test Score (SDMT-5 minutes)	The Symbol Digit Modalities Test (SDMT) is used to assess divided attention, visual scanning, tracking and motor speed. Using a reference key, the examinee has 90 seconds to pair specific numbers with given geometric figures. Because examinees can give either written or spoken responses, the test is well suited for use with individuals who have motor disabilities or speech disorders. Because it involves only geometric figures and numbers, the SDMT is relatively culture free as well and can be administered to individuals who do not speak English. It takes approximately 5 minutes to complete the entire test. Scoring involves summing the number of correct substitutions within the 90 second interval the max score is 110, where a higher score indicates a better memory.	Week 9 (after treatment ended)
Brief Visuospatial Memory test (BVMT-R-25 minutes)	This test is comprised of three memory trials (10 seconds each) followed by delayed recall after 25 minutes and a recognition trial. It has been widely used as a quick measure of visuospatial memory. The digital stimulus forms will be used (alternate form will be used at the end of the study to control for practice effect). Recall performance will record for each of the immediate recall trials (Trial 1, Trial 2, and Trial 3) and for the delayed recall trial (Delayed Recall). The study team will combine the recall scores to form three additional summary measures of learning and memory. Recognition Hits and False Alarms will be recorded during the delayed recognition task. Recognition Hits are calculated as the number of correct responses to target items, and Recognition False Alarms are calculated as the number of incorrect responses to nontarget items. Each trial is worth 0-12 points, so the total score is 0-36, a higher score indicates a better memory.	Week 9 (after treatment ended)
California Verbal Learning Test-Third Edition (CVLT-3-60 minutes)	The California Verbal Learning Test, Third Edition (CVLT-3) measures both recall and recognition of two lists of words (List A and List B) over a number of immediate and delayed memory trials. It provides an assessment of verbal learning and memory deficits in adults ages 16 - 90. Score of 0-16, where a lower score indicates worse memory, and a high score indicates better memory.	Week 9 (after treatment ended)
The Memory Complaint Scale (MCS-2 minute) score	The Memory Complaint Scale (MCS-2 min) is comprised of 14 items and is designed for subjective memory complaints.The test yields a total score with a classification in terms of memory complaint (MC) based on their score as follows: No MC (0-2), mild MC (3-6), moderate MC (7-10) or severe MC (11-14).	Week 9 (after treatment ended)

Collaborators and Investigators

• Sponsor: University of Michigan
• Investigators: Principal Investigator: Hala Darwish, PhD, University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2023
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 30, 2025

Study Registration Dates

• First Submitted: February 7, 2023
• First Submitted That Met QC Criteria: February 7, 2023
• First Posted (Actual): February 17, 2023

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 10, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Cognitive Behavioral Therapy; Affective Dysfunction; Modifiable lifestyle factors; Cognitive Rehabilitation Therapy; Long COVID (coronavirus disease)
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Cognition Disorders; Multiple Sclerosis; Brain Injuries; Brain Injuries, Traumatic; Cognitive Dysfunction; Neurocognitive Disorders
• Other Study ID Numbers: HUM00210257

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No