Health Education Programme Through Physical Exercise for People With Severe Mental Disorders (HEPPE-PSMI)

Development and Evaluation of a Health Education Programme Through Physical Exercise for the Development of Autonomous Physical Activity Habits in People With Severe Mental Disorders

The goal of this clinical trial is to [learn about, test, compare etc.] in individuals with severe mental disorders and obesity comorbid.

The main question[s] it aims to answer are:

• Are inflammatory activity, oxidative and vascular damage and metabolic mechanisms, as well as neurocognitive and functional performance, related to different physical exercise interventions?
• Do inflammatory, oxidative stress and cardiometabolic biomarkers predict neurocognitive improvement after physical activity training?

Participants will guided-exercise of moderate intensity and frecuency, and incentive of autonomous physical activity proposals by the specialist; guided physical activity group (GPAG), or (b) 12 weeks of an exercise program standard physical activity without guided and incentives; standard physical activity group (SPAG).

If there is a comparison group: Researchers will compare GPAG and SPAG to see if inflammatory, oxidative stress, and cardio-metabolic biomarkers improve neurocognitive performance after physical activity training

Study Overview

• Status: Completed
• Conditions: Obesity; Severe Mental Disorder
• Intervention / Treatment: Behavioral: Guided physical activity; Behavioral: Standard physical activity

Detailed Description

The psychiatric disorders and obesity comorbidity is related to neurocognitive impairment and inflammation. Exercise is crucial to improve and maintain healthy lifestyles. This randomized controlled trial tested the efficacy of aerobic exercise as promoter of neurocognitive improvement across psychiatric disorders and OB comorbid. Participants (n=29) received brief healthy lifestyle counseling and were randomized to 12 weeks of guided-exercise of moderate intensity and frequency, and incentive of autonomous physical activity proposals by the specialist; guided physical activity group (GPAG) (n=10) or 12 weeks of exercise standard physical activity without guided and incentives; standard physical activity group (SPAG) (n=19). Peripheral blood biomarkers of inflammation, oxidative stress, vascular mechanisms and metabolic activity, as well as neurocognitive and functional performance were assessed twice over after and before treatment. Mixed one-way analysis of variance and linear regression analyses were performed.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• MDD, BD and SZ were diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders - DSM-5 (APA, 2014).
• Participants with MDD and BD should meet the remission criteria (Tohen et al., 2009) of an acute affective episode, defined as Young Mania Rating Scale (YMRS) score ≤ 6 and Hamilton Rating Scale for Depression (HRSD) score ≤ 8, and individuals with SZ had to be clinically stable, defined as Positive and Negative Syndrome Scale (PANSS) score ≤ 36.
• The comorbid OB diagnosis was based on World Health Organization (WHO) criteria.
• Ability to understand study procedures and willingness to give written consent was required for participation.

For recruitment as HC

• Absence of physical illness
• Absence of pharmacological treatments
• Absence of family history of psychiatric disorders in first-degree relatives were required.
• Ability to understand study procedures and willingness to give written consent was required for participation.

Exclusion Criteria:

• current hospitalization
• documented cognitive impairment not secondary to psychiatric disorder (intellectual disability or major neurocognitive disorder, i.e. dementia)
• disability or inability that prevented understanding of the protocol
• current substance use disorders (except for nicotine)
• pregnancy
• intake of steroids
• corticosteroids, antioxidants, antibiotics, and immunologic therapies
• fever over 38°C
• history of vaccination within 4 weeks of the evaluation
• medical contraindications for exercise
• body mass index ≥ 40
• diastolic/systolic blood pressure ≥ 140/90
• resting heart rate ≥ 100.

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
Experimental: Guided physical activity group; Guided-exercise of moderate intensity and frecuency, and incentive of autonomous physical activity proposals by the specialist.	Behavioral: Guided physical activity; To achieve the European guidelines of 150 minutes by week of moderate intensity physical activity, participants randomized to the GPAG condition were prescribed three 60 minutes exercise sessions (five minutes of warm-up and five minutes of cool-down for a total of sixty minutes per session) per week for 12 weeks. Exercise consisted of brisk walking in urban and rural open spaces during which heart rate monitors were worn and participants were instructed to stay within their moderate intensity range. The incentives were different proposals for specific exercises to train the different musculoskeletal areas more comprehensively. Autonomous exercise was monitored offside the sessions through a series of weekly checkpoints.
Active Comparator: Standard physical activity group; Standard physical activity without guided and incentives.	Behavioral: Standard physical activity; Participants randomised to the SPAG performed their usual daily activities and continued with their daily routine. Both conditions were matched for duration of physical activity. Participants in both conditions were required to attend three on-site sessions by week over 12 weeks that served as checkpoints. Moreover, both conditions were provided with brief healthy lifestyle counseling at baseline.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Verbal learning and memory	Complutense Verbal Learning Test total immediate recall, short-term free recall and long-term free recall The higher scores mean a better outcome.	4 months
Cognitive flexibility	Wisconsin Card Sorting Test The higher scores mean a better outcome.	4 months
Verbal fluency	Animal naming test for phonemic and semantic fluency. The higher scores mean a better outcome.	4 months
Working memory	Trail Making Test The higher scores mean a better outcome.	4 months
Short-term memory	Complutense Verbal Learning Test total immediate recall, short-term free recall and long-term free recall The higher scores mean a better outcome.	4 months
Visual memory	Rey-Osterrieth Complex Figure Test figure two minutes after the copy and 20 minutes after the copy. The higher scores mean a better outcome.	4 months
Processing speed	Stroop Color and Word test color/word subtest The higher scores mean a better outcome.	4 months
Functional Assessment Short Test	Functional performance. The higher scores mean a better outcome.	4 months
Short Form-36 Health Survey questionnaire	Quality of life. The higher scores mean a better outcome.	4 months
World Health Organization Quality of Life brief scale	Quality of life. The higher scores mean a better outcome.	4 months
Inflammatory markers	Serum cytokine concentrations were determined using Luminex® X-MAP technology (Luminex Corp., Austin, TX, USA) based on flow cytometry. Sample processing and data analysis were performed according to the manufacturer's instructions. (Behring Nephelometer II, Dade Behring, Inc., Newark, DE, USA)..	4 months
Oxidative stress markers	Oxidative stress in leukocytes was evaluated using fluorimetry techniques with a fluoroscan (Synergy MX). In total, 100 000 cells were plated in each well of 96-well plates and incubated for 30 min at 37 °C with the corresponding fluorochromes, as follows: dichlorofluorescein diacetate to measure reactive oxygen species (ROS) production (485 nm excitation, 535 nm emission), MitoSOX to measure mitochondrial ROS (mROS) (510 nm excitation, 580 nm emission), tetramethylrodamin methyl ester to assess mitochondrial membrane potential (552 nm excitation, 574 nm emission), nonylacridin orange mitochondrial mass (495 nm excitation, 519 nm emission), and 5-chloromethylfluorescein diacetate to measure intracellular glutathione (492 nm excitation, 517 nm emission). The monocyte cell line U-937 was used as an internal control to avoid potential fluctuations in fluorescence over time.	4 months
Adhesion molecules markers	Serum lipid peroxidation levels were measured using a commercial thiobarbituric acid reactive substances (TBARS) kit according to the manufacturer's instructions (Olympus, Hamburg, Germany). A Luminex 200 flow analyzer system (Austin, TX, USA) was employed to analyze adhesion molecules in serum. To measure immunological markers, citrated blood samples were incubated with dextran (3%) for 45 min to isolate human polymorphonuclear leukocytes (PMNs). The supernatant was layered over Ficoll-Hypaque (GE Healthcare, Barcelona, Spain) and centrifuged for 25 min at room temperature at 650g. Lysis buffer was added to the remaining erythrocytes in the pellet, which were incubated at room temperature for 5 min and then spun at 240g for 5 min. PMNs were rinsed twice and resuspended at 37 ℃ in Hanks' balanced salt solution (Sigma Aldrich, MO). Scepter 2.0 cell counters (Millipore, MA, USA) was employed to count cells	4 months
Metabolic markers	Under aseptic conditions, fasting venous blood samples were collected between 8 and 9 am to measure.	4 months
Maximum heart rate	Measured with a watch-shaped device that was worn on the wrist and captured the beats per minute.	4 months
Systolic pressure/diastolic pressure	Measured on the right arm using an automatic sphygmomanometer with participants in the sitting position after resting for 5 minutes.	4 months
Waist circumference	Measured in the standing position at the end of normal expiration and at the midway between the inferior costal margin and the superior border of the iliac crest.	4 months

Collaborators and Investigators

• Sponsor: Fundación para la Investigación del Hospital Clínico de Valencia
• Investigators: Principal Investigator: Rafael Tabarés-Seisdedos, Consorcio Centro de Investigación Biomédica en Red (CIBER)

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2016
• Primary Completion (Actual): June 30, 2016
• Study Completion (Actual): June 30, 2016

Study Registration Dates

• First Submitted: September 5, 2023
• First Submitted That Met QC Criteria: October 3, 2023
• First Posted (Actual): October 6, 2023

Study Record Updates

• Last Update Posted (Actual): October 6, 2023
• Last Update Submitted That Met QC Criteria: October 3, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Oxidative stress; Inflammation; Exercise; Obesity; Neurocognition; Metabolic activity; Vascular damage; Mental illnesses
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Psychotic Disorders; Mental Disorders
• Other Study ID Numbers: Physical exercise programme

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