Improving Cognition Via Exercise in Schizophrenia

• ClinicalTrials.gov Identifier: NCT03270098
• Recruitment Status: Completed
• First Posted: September 1, 2017
• Last Update Posted: April 14, 2023
• Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborators: University of North Carolina, Chapel Hill; Stanford University; Augusta University; Columbia University; National Institute of Mental Health (NIMH)
• Information provided by (Responsible Party): David Kimhy, Icahn School of Medicine at Mount Sinai

Study Description

Brief Summary:

People with schizophrenia display a broad range of cognitive impairments that have been identified as major determinants of poor functioning and disability. Also, people with schizophrenia are at increased risk for suicide, with approximately 40-50% of individuals attempting to take their own lives during their lifetime. The goal of the proposed study is to examine the impact of remote exercise training on cognition, suicide risk, daily functioning, and biomarkers of cognitive change and suicidality in people with schizophrenia.

Condition or disease	Intervention/treatment	Phase
Schizophrenia and Related Disorders	Behavioral: Aerobic Exercise; Behavioral: Stretching and Toning Exercise	Not Applicable

Detailed Description:

The goal of the proposed study is to examine the impact of remote exercise training on cognitive functioning in people with schizophrenia. People with schizophrenia display a broad range of cognitive impairments that have been identified as major determinants of poor functional outcome and disability, thus representing an important public health concern and a target for interventions. At present, available treatments offer only minimal to limited benefits to ameliorate these deficits. Extensive animal and human research literatures converge in supporting the positive influence of aerobic exercise training on cognitive functioning. Preliminary data indicate that aerobic exercise training is effective in improving cognitive functioning in people with schizophrenia. However, previous studies employed small samples, focused on a single or limited range of cognitive domains, and/or collected insufficient information on daily functioning or putative biomarkers underlying cognitive change. Supported by supplement funding from NIMH, the goal of the proposed study is also to explore the impact of remote exercise training on suicide risk in individuals with schizophrenia. People with schizophrenia are at increased risk for suicide, with approximately 40-50% of individuals attempting to take their own lives during their lifetime, and an estimated 5-10% actually being successful in completing suicide. This highly elevated risk represents a serious public health concern and an important target for interventions. However, available treatments offer only minimal to limited benefits to ameliorate this risk. Extensive animal and human research literatures converge in supporting the positive influence of AE training on a number of predictors of suicide risk including depressed mood, sleep difficulties, and poor cognition. Yet, at present there are no studies directly examining the impact of AE on suicide risk in this population.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 104 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This study is a single-blind, parallel assignment, multi-site randomized clinical trial designed to examine the impact of exercise on cognition, daily functioning, and biomarkers of cognitive change in people with schizophrenia.
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Improving Cognition Via Exercise in Schizophrenia
• Actual Study Start Date: April 26, 2018
• Actual Primary Completion Date: January 31, 2023
• Actual Study Completion Date: January 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Aerobic Exercise; Using trainer-led video calls with traditional callisthenic body movements (e.g., jumping jacks, burpees, etc.)	Behavioral: Aerobic Exercise; Trainer-led one hour aerobic exercise sessions, three times per week, over 12 weeks.
Active Comparator: Stretching and Toning Exercise; Using trainer-led video calls with stretching and toning exercises.	Behavioral: Stretching and Toning Exercise; Trainer-led one hour stretching-and-toning exercise sessions, three times per week, over 12 weeks.

Outcome Measures

Primary Outcome Measures :

1. Change in the MATRICS Consensus Cognitive Battery (MCCB) [ Time Frame: Baseline and 12 weeks ]
   The MCCB is a standardized battery designed to measure cognitive functioning in people with schizophrenia. The MCCB is represented as a composite T score. Change in the MCCB at 12 weeks as compared to baseline.
2. Change in VO2Max [ Time Frame: Baseline and 12 weeks ]
   VO2Max (maximal oxygen consumption) is an index of the ability to consume oxygen and is a key indicator of aerobic fitness. Change in the VO2Max at 12 weeks as compared to baseline.

Secondary Outcome Measures :

1. Change in the Specific Levels of Functioning Scale (SLOF) [ Time Frame: Baseline and 12 weeks ]
   The SLOF is a 43-item survey assessing multiple domains of daily functioning. Total score range from 43 to 215, with higher scores indicating better the overall functioning. Change in the SLOF at 12 weeks as compared to baseline.
2. Change in the UCSD Performance-based Skills Assessment (UPSA) [ Time Frame: Baseline and 12 weeks ]
   The UPSA is performance-based measure of real-world daily functioning abilities. Participants receive scores for multiple domains, which are summed to create a summary score ranging from 0 to 100 with higher score indicating better overall functioning. Change in the UPSA at 12 weeks as compared to baseline.
3. Change in the Schizophrenia Cognition Rating Scale (SCoRS) [ Time Frame: Baseline and 12 weeks ]
   The SCoRS is a 20-item clinician-administered interview assessing cognition-related daily functioning. Each item rated on a 4-point scale ranging from "no impairment" to "severe impairment". Total scores range from 20-80, with higher score indicating poorer functioning. Change in the SCoRS at 12 weeks as compared to baseline.
4. Serum BDNF [ Time Frame: Baseline and 12 weeks ]
   BDNF is extracted from blood samples and serves as a biomarker of exercise-related cognitive changes. Change in the BDNF at 12 weeks as compared to baseline.
5. Change in Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Baseline and 12 weeks ]
   The C-SSRS is a semi-structured interview that measures 4 suicide risk related domains: ideation severity, ideation intensity, behavior, and lethality. Full scale from 1-10, with higher score indicating more suicidal ideation and behavior. Change in the C-SSRS at 12 weeks as compared to baseline.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• A DSM-V diagnosis of schizophrenia, schizoaffective, or schizophreniform disorder.
• Age 18-55 years.
• Taking antipsychotic medication for at least 8 weeks and on current doses for 4 weeks, and/or injectable depot antipsychotics with no change in the last 3 months.
• Capacity to understand all the potential risks and benefits of the study.
• Medically cleared by a physician to take part in VO2max tests and aerobic exercise training or stretching-and-toning exercise training.

Exclusion Criteria:

• A DSM-V diagnosis of alcohol/substance abuse (except nicotine) within the last month or a diagnosis of alcohol/substance dependence (except nicotine) within the last 6 months
• Initiation of anti-depressants, mood stabilizers, or other medications known to impact cognition in previous 4 weeks or any change in doses during this period.
• History of seizures/head trauma with loss of consciousness (>10 minutes) resulting in cognitive sequelae.
• Significant clinical abnormalities in physical examination, lab assessments, or ECG.
• Neurological/medical conditions that could interfere with study participation (e.g., unstable cardiac disease, stuttering).
• Body Mass Index (BMI) ≥ 40.
• Untreated hyper- or hypothyroidism.
• Being pregnant or nursing.
• Serious homicidal/suicidal risk (past 6 months).
• "Moderate" or more severe conceptual disorganization (PANSS≥4).
• Poor English reading ability (WTAR<7).
• Participation in a study with cognitive assessment in the past 3 months.
• Serious homicidal risk (past 6 months)

Contacts and Locations

Locations

United States, California

Stanford University

Stanford, California, United States, 94305

United States, Georgia

Augusta University

Augusta, Georgia, United States, 30912

United States, New York

Icahn School of Medicine at Mount Sinai

New York, New York, United States, 10029

United States, North Carolina

University of North Carolina

Chapel Hill, North Carolina, United States, 27599

Sponsors and Collaborators

Icahn School of Medicine at Mount Sinai

University of North Carolina, Chapel Hill

Stanford University

Augusta University

Columbia University

National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: David Kimhy, PhD; Icahn School of Medicine at Mount Sinai
• Principal Investigator: T. Scott Stroup, MD, MPH; Columbia University

More Information

Publications:

Kimhy D, Vakhrusheva J, Bartels MN, Armstrong HF, Ballon JS, Khan S, Chang RW, Hansen MC, Ayanruoh L, Lister A, Castren E, Smith EE, Sloan RP. The Impact of Aerobic Exercise on Brain-Derived Neurotrophic Factor and Neurocognition in Individuals With Schizophrenia: A Single-Blind, Randomized Clinical Trial. Schizophr Bull. 2015 Jul;41(4):859-68. doi: 10.1093/schbul/sbv022. Epub 2015 Mar 23.

Kimhy D, Lauriola V, Bartels MN, Armstrong HF, Vakhrusheva J, Ballon JS, Sloan RP. Aerobic exercise for cognitive deficits in schizophrenia - The impact of frequency, duration, and fidelity with target training intensity. Schizophr Res. 2016 Apr;172(1-3):213-5. doi: 10.1016/j.schres.2016.01.055. Epub 2016 Feb 3. No abstract available.

Kimhy D, Khan S, Ayanrouh L, Chang RW, Hansen MC, Lister A, Ballon JS, Vakhrusheva J, Armstrong HF, Bartels MN, Sloan RP. Use of Active-Play Video Games to Enhance Aerobic Fitness in Schizophrenia: Feasibility, Safety, and Adherence. Psychiatr Serv. 2016 Feb;67(2):240-3. doi: 10.1176/appi.ps.201400523. Epub 2015 Oct 1.

Armstrong HF, Bartels MN, Paslavski O, Cain D, Shoval HA, Ballon JS, Khan S, Sloan RP, Kimhy D. The impact of aerobic exercise training on cardiopulmonary functioning in individuals with schizophrenia. Schizophr Res. 2016 May;173(1-2):116-7. doi: 10.1016/j.schres.2016.03.009. Epub 2016 Mar 11. No abstract available.

Vakhrusheva J, Marino B, Stroup TS, Kimhy D. Aerobic Exercise in People with Schizophrenia: Neural and Neurocognitive Benefits. Curr Behav Neurosci Rep. 2016 Jun;3(2):165-175. doi: 10.1007/s40473-016-0077-2. Epub 2016 Apr 4.

Kimhy D, Vakhrusheva J, Bartels MN, Armstrong HF, Ballon JS, Khan S, Chang RW, Hansen MC, Ayanruoh L, Smith EE, Sloan RP. Aerobic fitness and body mass index in individuals with schizophrenia: Implications for neurocognition and daily functioning. Psychiatry Res. 2014 Dec 30;220(3):784-91. doi: 10.1016/j.psychres.2014.08.052. Epub 2014 Sep 3.

Ospina LH, Wall M, Jarskog LF, Ballon JS, McEvoy J, Bartels MN, Buchsbaum R, Sloan RP, Stroup TS, Kimhy D. Improving Cognition via Exercise (ICE): Study Protocol for a Multi-Site, Parallel-Group, Single-Blind, Randomized Clinical Trial Examining the Efficacy of Aerobic Exercise to Improve Neurocognition, Daily Functioning, and Biomarkers of Cognitive Change in Individuals with Schizophrenia. J Psychiatr Brain Sci. 2019;4:e190020. doi: 10.20900/jpbs.20190020. Epub 2019 Dec 30.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Beck-Felts K, Goodman M, Ospina LH, Wall M, McEvoy J, Jarskog LF, Ballon JS, Bartels MN, Buchsbaum R, Sloan RP, Stroup TS, Kimhy D. Suicide Reduction in Schizophrenia via Exercise (SUnRISE): study protocol for a multi-site, single-blind, randomized clinical trial of aerobic exercise for suicide risk reduction in individuals with schizophrenia. Trials. 2020 Oct 21;21(1):871. doi: 10.1186/s13063-020-04788-z.

• Responsible Party: David Kimhy, Associate Professor, Psychiatry, Icahn School of Medicine at Mount Sinai
• ClinicalTrials.gov Identifier: NCT03270098
• Other Study ID Numbers: GCO 17-1511; 1R01MH110623-01A1 ( U.S. NIH Grant/Contract ); 3R01MH110623-03S1 ( U.S. NIH Grant/Contract )
• First Posted: September 1, 2017
• Last Update Posted: April 14, 2023
• Last Verified: April 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by David Kimhy, Icahn School of Medicine at Mount Sinai:

Schizophrenia; Aerobic Exercise; Cognition; Daily Functioning; Biomarkers; Brain Derived Neurotrophic Factor; Suicide Risk

Additional relevant MeSH terms:

Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders