Functionality and Neurocognition in Patients With Bipolar Disorder After a Physical-exercise Program (FINEXT-BD Study)

Study Overview
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Brief Summary
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This is a study that aimed to deep in the physiopathology of BD and see how, through potential modifiable areas of the patients' lifestyle, the prognosis and evolution of the pathology can be improved.

Detailed Description
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Randomized interventionist study (ratio 1:1) with two parallel branches, blinded by evaluators (the evaluator does not know the branch of treatment to which the patient belongs )to evaluate if an individualized moderate-to-vigorous physical exercise intensity program as adjuvant therapy to standard drug therapy will improve the functional and neuropsychological status of patients with Bipolar Disorder. The effectiveness of the intervention will be assessed by an extensive battery of clinical tests, physical parameters (e.g. brain structure changes measured by optical coherence tomography) and biological parameters (inflammation, oxidative stress and neurotrophic factors). The total sample of the study will be 80 patients and a sample of 40 controls (individuals without psychiatric pathology). The sample of patients will be divided into 40 patients in each group at random. In the intervention group, a supervised physical exercise treatment by high-intensity interval training (HIT) will be performed during 16 weeks with 2 sessions per week (32 sessions in total).Three visits will be made in both groups: baseline visit at the beginning of the study, at 4 months (at the end of the intervention) and at 10 months (6 months after the end of the intervention)

Official Title
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Functionality and Neurocognition in Patients With Bipolar Disorder After a Physical-exercise Program (FINEXT-BD Study): Protocol of a Randomized Interventionist Program

Conditions
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Bipolar Disorder

Intervention / Treatment
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* Other: Physical exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed with bipolar disorder type I according to the criteria of the DSM-5 manual, diagnosis made by structured interview SCID-P. The study includes patients with first episode and multiple episodes. At the beginning of the study they must be in euthymia, that is, there will be no current diagnosis of manic, hypomanic or depressive episode. Relapses during follow-up and the presence of subindromial symptoms at any time will not result in exclusion from the study. Patients may be treated with any treatment according to clinical guidelines. Age: 18-65 years Speak Spanish correctly Informed consent for the study of the patient Exclusion Criteria: Presence of organic diseases of the central nervous system (CNS) or history of head trauma with loss of consciousness Intellectual disability. Acute inflammatory disease Treatment with anti-inflammatory drugs during the week prior to sample taking Pervasive developmental disorders. Pregnancy and lactation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Longitudinal, interventional, randomized, controlled, simple-blind clinical trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control (TAU)<br>patients without any intervention + treatment as usual (TAU) | |
| Experimental: PE intervention+TAU<br>Physical exercise (PE) intervention + treatment as usual (TAU) | Other: Physical exercise<br>* The experimental group will receive supervised physical exercise treatment by high-intensity interval training (HIT), alternating high and moderate intensities (20 min). The participants will exercise two non-consecutive days per week for 16 weeks under supervision by exercise specialists.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Functionality measured through the scale FAST (4 months) | The Functioning Assessment Short Test is a brief instrument designed to assess functional impairment in severe mental disorders. The 24 items of the scale cover six specific areas of functioning: autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships, and leisure time. | Change at the end of the training period (4 months) | 
| Patient Functionality measured through the scale FAST (10 months) | The Functioning Assessment Short Test is a brief instrument designed to assess functional impairment in severe mental disorders. The 24 items of the scale cover six specific areas of functioning: autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships, and leisure time. | Changes after 10 months | 
| Patient Functionality measured through the scale GAF (4 months) | Global Assessment of Functioning (GAF):This scale evaluates with a score from 0 to 100 the level of functioning and the severity of the patient's symptoms, the higher values corresponding to better overall functionality. | Change at the end of the training period (4 months) | 
| Patient Functionality measured through the scale GAF (10 months) | Global Assessment of Functioning (GAF):This scale evaluates with a score from 0 to 100 the level of functioning and the severity of the patient's symptoms, the higher values corresponding to better overall functionality. | Changes after 10 months | 
| Patient Functionality measured through the Strauss-Carpenter scale (4 months) | Strauss-Carpenter scale consists of four items rated from 0 to 4 on a Likert-type scale and yields a total score that is calculated by the addition of all item scores: the higher the score, the better is the prognosis. | Change at the end of the training period (4 months) | 
| Patient Functionality measured through the Strauss-Carpenter scale (10) months) | Strauss-Carpenter scale consists of four items rated from 0 to 4 on a Likert-type scale and yields a total score that is calculated by the addition of all item scores: the higher the score, the better is the prognosis. | Changes after 10 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TrkB-FL (4 months) | Expression of BDNF: TrkB-FL | Change at the end of the training period (4 months) | 
| TrkB-FL (10 months) | Expression of BDNF: TrkB-FL | Changes after 10 months | 
| TrkB-T (4 months) | Expression of BDNF:TrkB-T | Change at the end of the training period (4 months) | 
| TrkB-T (10 months) | Expression of BDNF:TrkB-T | Changes after 10 months | 
| BDNF (4 months) | Peripheral BDNF levels | Change at the end of the training period (4 months) | 
| BDNF (10 months) | Peripheral BDNF levels | Changes after 10 months | 
| Presence of depressive symptoms (4 months) | Hamilton Depression Scale (HDRS-21) | Change at the end of the training period (4 months) | 
| Presence of depressive symptoms (10 months) | Hamilton Depression Scale (HDRS-21) | Changes after 10 months | 
| VO2Peak in CPET (4 months) | Value of VO2Peak (L min-1) in cardiopulmonary exercise test (CPET) | Change at the end of the training period (4 months) | 
| VO2Peak in CPET (10 months) | Value of VO2Peak (L min-1) in cardiopulmonary exercise test (CPET) | Changes after 10 months | 
| Relative VO2Peak in CPET (4 months) | Value of relative VO2Peak (mL kg-1 min-1) in cardiopulmonary exercise test (CPET) | Change at the end of the training period (4 months) | 
| Relative VO2Peak in CPET (10 months) | Value of relative VO2Peak (mL kg-1 min-1) in cardiopulmonary exercise test (CPET) | Changes after 10 months | 
| METs in CPET (4 months) | Value of metabolic equivalents in cardiopulmonary exercise test (CPET) | Change at the end of the training period (4 months) | 
| METs in CPET (10 months) | Value of metabolic equivalents in cardiopulmonary exercise test (CPET) | Changes after 10 months | 
| VT1 and VT2 in CPET (4 months) | Value of first and second ventilatory threshold (VT1 and VT2)(mL kg-1 min-1) metabolic equivalents in cardiopulmonary exercise test (CPET) | Change at the end of the training period (4 months) | 
| VT1 and VT2 in CPET(10 months) | Value of first and second ventilatory threshold (VT1 and VT2)(mL kg-1 min-1) metabolic equivalents in cardiopulmonary exercise test (CPET) | Changes after 10 months | 
| HRpeak in CPET (4 months) | Value of HRpeak in cardiopulmonary exercise test (CPET) | Change at the end of the training period (4 months) | 
| HRpeak in CPET (10 months) | Value of HRpeak in cardiopulmonary exercise test (CPET) | Changes after 10 months | 
| OCT Study of the retina by optical tomography (4 months) | RFNL, GCL and IPL thickness in the two eyes, with each layer divided into segments: overall, temporal, nasal, superior and inferior. | Change at the end of the training period (4 months) | 
| OCT Study of the retina by optical (10 months) | RFNL, GCL and IPL thickness in the two eyes, with each layer divided into segments: overall, temporal, nasal, superior and inferior. | Changes after 10 months | 
| Muscle mass (4 months) | Anthropometric measures muscle mass (g) | Change at the end of the training period (4 months) | 
| Muscle mass (10 months) | Anthropometric measures muscle mass (g) | Changes after 10 months | 
| Fat mass (%)(4 months) | Anthropometric measures Fat mass (%) | Change at the end of the training period (4 months) | 
| Fat mass (%) (10 months) | Anthropometric measures Fat mass (%) | Changes after 10 months | 
| Bone mineral content (4 months) | Anthropometric measures: Bone mineral density (g/cm^2) shall be determined by Dual Energy X-Ray Absorptiometry (DXA). | Change at the end of the training period (4 months) | 
| Bone mineral content (4 months) | Anthropometric measures: Bone mineral density (g/cm^2) shall be determined by Dual Energy X-Ray Absorptiometry (DXA). | Changes after 10 months | 
| Appendicular muscle mass (4months) | Anthropometric measures: appendicular muscle mass (g) will also be determined by adding up the muscle mass of both arms and legs. | Change at the end of the training period (4 months) | 
| Appendicular muscle mass (10 months) | Anthropometric measures: appendicular muscle mass (g) will also be determined by adding up the muscle mass of both arms and legs. | Changes after 10 months | 
| Oxidative stress (4 months) | Oxidative stress: Total Antioxidant Status (TAS), Glutathione peroxidase (GPx) y - Glutathione (GSH), Lipid Peroxidation (TBARS) y Nitrite (NO2) | Change at the end of the training period (4 months) | 
| Oxidative stress (10 months) | Oxidative stress: Total Antioxidant Status (TAS), Glutathione peroxidase (GPx) y - Glutathione (GSH), Lipid Peroxidation (TBARS) y Nitrite (NO2) | Changes after 10 months | 
| Inflammation (4 months) | Cytokine levels: IL6 and prostaglandin Levels PGE2 | Change at the end of the training period (4 months) | 
| Inflammation (10 months) | Cytokine levels: IL6 and prostaglandin Levels PGE2 | Changes after 10 months | 
| Manic symptoms using the (YMRS) (4 months) | Young Mania Rating Scale (YMRS): The total score ranges from 0-60, with the status of euthymia being classified as getting 6 or fewer points, hypomania as getting 12 or more points, and mania as getting between 20 and 60 points. | Change at the end of the training period (4 months) | 
| Manic symptoms using the (YMRS) (10 months) | Young Mania Rating Scale (YMRS): The total score ranges from 0-60, with the status of euthymia being classified as getting 6 or fewer points, hypomania as getting 12 or more points, and mania as getting between 20 and 60 points. | Changes after 10 months | 
| Body mass (4 months) | Physical parameters: Body mass (kg) | Change at the end of the training period (4 months) | 
| Body mass (10 months) | Physical parameters: Body mass (kg) | Changes after 10 months | 
| Height (4 months) | Physical parameters: Height (cm) | Change at the end of the training period (4 months) | 
| Height (10 months) | Physical parameters: Height (cm) | Changes after 10 months | 
| BMI (4 months) | Physical parameters: Body mass index (kg/m2) | Change at the end of the training period (4 months) | 
| BMI (10 months) | Physical parameters: Body mass index (kg/m2) | Changes after 10 months | 
| Waist circumference (4 months) | Physical parameters: Waist circumference (cm) | Change at the end of the training period (4 months) | 
| Waist circumference (4 months) | Physical parameters: Waist circumference (cm) | Changes after 10 months | 
| SBP and DBP (4 months) | Physical parameters: Systolic and diastolic blood pressure (mm Hg) measured taken from the right arm in a seated and relaxed position by using a life-support monitor | Change at the end of the training period (4 months) | 
| SBP and DBP (10 months) | Physical parameters: Systolic and diastolic blood pressure (mm Hg) measured taken from the right arm in a seated and relaxed position by using a life-support monitor | Changes after 10 months | 
| TG (4 months) | Physical parameters: Serum levels of triglycerides (mg/dl ) | Change at the end of the training period (4 months) | 
| TG (10 months) | Physical parameters: Serum levels of triglycerides (mg/dl ) | Changes after 10 months | 
| Glucose (4 months) | Physical parameters: Glucose (mg/dl) | Change at the end of the training period (4 months) | 
| Glucose (10 months) | Physical parameters: Glucose (mg/dl) | Changes after 10 months | 
| HDL (4 months) | Physical parameters: HDL colesterol (mg/dl) | Change at the end of the training period (4 months) | 
| HDL (10 months) | Physical parameters: HDL colesterol (mg/dl) | Changes after 10 months | 
| Patient symptom severity measured through the scale CGI (4 months) | The Clinical Global Impression Scale (CGI): consists of two subscales. Each subscale has a single item scored between 0, not evaluated, to 7 which corresponds to the maximum severity (severity subscale) or to a state of no improvement and aggravated worsening of the symptomatology (improvement subscale). | Change at the end of the training period (4 months) | 
| Patient symptom severity measured through the scale CGI (10 months) | The Clinical Global Impression Scale (CGI): consists of two subscales. Each subscale has a single item scored between 0, not evaluated, to 7 which corresponds to the maximum severity (severity subscale) or to a state of no improvement and aggravated worsening of the symptomatology (improvement subscale). | Changes after 10 months | 
| Cognitive functioning measured through CVLT (10 months) | California Verbal Learning Test | Changes after 10 months | 
| Cognitive functioning measured through CVLT (4 months) | California Verbal Learning Test | Change at the end of the training period (4 months) | 
| Cognitive functioning measured through WSCT (10 months) | Computerized version of Wisconsin Card Sorting Test: This test consists of cards depicting simple geometric figures that vary in color, shape, and number. Examinees must sort cards in accordance with one of three viable rules, i.e., according to the color, shape, or number of the depicted objects | Changes after 10 months | 
| Cognitive functioning measured through WSCT (4 months) | Computerized version of Wisconsin Card Sorting Test: This test consists of cards depicting simple geometric figures that vary in color, shape, and number. Examinees must sort cards in accordance with one of three viable rules, i.e., according to the color, shape, or number of the depicted objects | Change at the end of the training period (4 months) | 
| Cognitive functioning measured through (SCWT) (10 months) | The Stroop Color and Word Test: Individuals are required to read three different tables as fast as possible. Two of them represent the congruous condition in which participants are required to read names of colors (color-words) printed in black ink (W) and name different color patches (C). Conversely, in the third table, named color-word (CW) condition, color-words are printed in an inconsistent color ink. | Changes after 10 months | 
| Cognitive functioning measured through (SCWT) (4 months) | The Stroop Color and Word Test: Individuals are required to read three different tables as fast as possible. Two of them represent the congruous condition in which participants are required to read names of colors (color-words) printed in black ink (W) and name different color patches (C). Conversely, in the third table, named color-word (CW) condition, color-words are printed in an inconsistent color ink. | Change at the end of the training period (4 months) |