Braining- Aerobic Physical Activity as Add on Treatment in Bipolar Depression

Study Overview
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Brief Summary
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Hypothesis: the hypothesis of the study is that aerobic physical exercise (PE) performed with the method Braining accelerates recovery from bipolar depression as well as improves psychiatric and somatic health in individuals with bipolar depression Method: a randomized controlled trial with 54 patients with bipolar depression are randomized to 12 weeks of either 1) supervised aerobic PE 3 times/week, 2) supervised relaxation/stretching 3 times/week or 3) information about PE but no supervised activity.

Detailed Description
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The hypothesis of this study is that adding aerobic PE might accelerate recovery, reduce negative side effects, improve mental wellbeing and function, increase long term prevention against relapsing bipolar episodes and reduce risk for complications such as cardiovascular disease in patients with bipolar disorder. Furthermore the study aims to evaluate if the effect of PE is linked to biological factors such as genetical factors, stress hormone levels, level of inflammation and other biological markers for health and disease that can be measured in standard blood samples. Patients diagnosed with bipolar disorder with ongoing depression are invited to participate in the study at regular visits in the psychiatric clinic. All study participants are medicated with mood stabilizers according to routine treatment and receive regular treatment for bipolar depression. After informed consent the study participants will be randomized to one of three groups 1) moderate to vigorous PE group training together with psychiatric staff three times per week 2) relaxing and stretching exercises group training together with psychiatric staff three times per week 3) information about PE and relaxation but no supervised PE or relaxation/stretching, for the 12 weeks of the study period. BEFORE: The first week consists of pre-test including interview regarding medical history and physical and psychiatric examination, ECG and blood samples. To measure level of physical activity the participants wear an activity monitor, Actiheart, that continuously registers physical activity for 7 days. The study participants will also fill out different questionnaires regarding general health and psychiatric symptoms. STUDY PERIOD: During the 12 weeks long study period the participants fill out an activity questionnaire and health questionnaires once a week. AFTER: during the twelfth week of the study period evaluation is being performed with repetition of the physical and psychiatric examination, blood samples and questionnaires. After 1, 2 and 3 years after the exercise period the questionnaires are repeated. Blood samples are repeated one year after the study period.

Official Title
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Braining - A Randomized Controlled Study on Moderate-vigorous Aerobic Physical Exercise (PE) as an add-on Treatment in Bipolar Disorder. Effects on Recovery Time and Long-term Prevention From Bipolar Depression

Conditions
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Bipolar Disorder, Bipolar Depression, Bipolar I Disorder, Bipolar II Disorder, Bipolar Affective Disorder; Remission in, Bipolar Affective Disorder, Currently Depressed, Moderate

Intervention / Treatment
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* Behavioral: Aerobic Physical Exercise
* Behavioral: Relaxing Physical Exercise
* Behavioral: Information about physical exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients at Psychiatry Southwest, Karolinska University Hospital Region Stockholm Sweden. Bipolar disorder Ongoing depression Exclusion Criteria: Severe psychiatric disorder such as mania and psychosis Medical conditions such as heart- and lung diseases where PE is contraindicated. Unable to understand written and spoken Swedish language.

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomized controlled trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Braining high intensity<br>Moderate to vigorous physical exercise, supervised by psychiatric staff 3 times per week | Behavioral: Aerobic Physical Exercise<br>* Moderate to vigorous physical exercise 30-45 minutes in a group setting led by psychiatric staff, 3 times per week for 12 weeks<br>|
| Active Comparator: Braining relaxing exercise<br>Relaxation, light yoga or stretching exercise, supervised by psychiatric staff 3 times per week | Behavioral: Relaxing Physical Exercise<br>* Relaxing exercises (stretching, light yoga) 30-45 minutes in a group setting led by psychiatric staff, 3 times per week for 12 weeks<br>|
| Active Comparator: Information about physical exercise<br>Written and oral information about health benefits from physical exercise, provided by researcher on one occasion. | Behavioral: Information about physical exercise<br>* Written and oral information about physical exercise recommendations, on one occasion, by researcher<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PHQ-9 (Patient Health Questionnaire - 9 items) | Self rated depressive symptoms. Minimum value 0, maximum value 27, where higher values indicate more depressive symptoms. | Change from inclusion to follow up 3 months after inclusion | 
| PHQ-9 (Patient Health Questionnaire - 9 items) | Self rated depressive symptoms. Minimum value 0, maximum value 27, where higher values indicate more depressive symptoms. | At follow up 12 months after intervention. | 
| PHQ-9 (Patient Health Questionnaire - 9 items) | Self rated depressive symptoms. Minimum value 0, maximum value 27, where higher values indicate more depressive symptoms. | At follow up 24 months after intervention. | 
| PHQ-9 (Patient Health Questionnaire - 9 items) | Self rated depressive symptoms. Minimum value 0, maximum value 27, where higher values indicate more depressive symptoms. | At follow up 36 months after intervention. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AS-18 (Affective self rating scale) | Self-assessment of symptoms of depression and hypomania/mania. 9 items for depression and 9 items for mania. Score 0-72. A score of over 10 on the depressive or manic/hypomanic subscale should give rise to suspicion of ongoing depression and hypomania/mania respectively. Scores of over 10 on both the depressive and manic/hypomanic scale at the same time give may indicate an affective mixed state. | Change from inclusion to follow up 3 months after inclusion | 
| AS-18 (Affective self rating scale) | Self-assessment of symptoms of depression and hypomania/mania. 9 items for depression and 9 items for mania. Score 0-72. A score of over 10 on the depressive or manic/hypomanic subscale should give rise to suspicion of ongoing depression and hypomania/mania respectively. Scores of over 10 on both the depressive and manic/hypomanic scale at the same time give may indicate an affective mixed state. | At follow up 12 months after intervention. | 
| AS-18 (Affective self rating scale) | Self-assessment of symptoms of depression and hypomania/mania. 9 items for depression and 9 items for mania. Score 0-72. A score of over 10 on the depressive or manic/hypomanic subscale should give rise to suspicion of ongoing depression and hypomania/mania respectively. Scores of over 10 on both the depressive and manic/hypomanic scale at the same time give may indicate an affective mixed state. | At follow up 24 months after intervention. | 
| AS-18 (Affective self rating scale) | Self-assessment of symptoms of depression and hypomania/mania. 9 items for depression and 9 items for mania. Score 0-72. A score of over 10 on the depressive or manic/hypomanic subscale should give rise to suspicion of ongoing depression and hypomania/mania respectively. Scores of over 10 on both the depressive and manic/hypomanic scale at the same time give may indicate an affective mixed state. | At follow up 36 months after intervention. | 
| YMRS (Young Ziegler Mania Rating Scale) | Interviewer-rated scale. Includes 11 items; seven are rated from 0 (absent) to 4; four from 0 to 8; total scores range from 0 to 60. A higher value indicates worse symptoms of hypomania/mania. | change from inclusion to follow up 3 months after inclusion | 
| YMRS (Young Ziegler Mania Rating Scale) | Interviewer-rated scale. Includes 11 items; seven are rated from 0 (absent) to 4; four from 0 to 8; total scores range from 0 to 60. A higher value indicates worse symptoms of hypomania/mania. | At follow up 12 months after intervention. | 
| YMRS (Young Ziegler Mania Rating Scale) | Interviewer-rated scale. Includes 11 items; seven are rated from 0 (absent) to 4; four from 0 to 8; total scores range from 0 to 60. A higher value indicates worse symptoms of hypomania/mania. | At follow up 24 months after intervention. | 
| YMRS (Young Ziegler Mania Rating Scale) | Interviewer-rated scale. Includes 11 items; seven are rated from 0 (absent) to 4; four from 0 to 8; total scores range from 0 to 60. A higher value indicates worse symptoms of hypomania/mania. | At follow up 36 months after intervention. | 
| CGI-S (Clinical Global Impressions - Severity Scale) | A one-item clinician assessed measure which evaluates the severity of psychopathology from 1 to 7, where 1 is 'normal' and 7 is 'among the most extremely ill patients' by the question Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?. | change from inclusion to follow up 3 months after inclusion | 
| CGI-S (Clinical Global Impressions - Severity Scale) | A one-item clinician assessed measure which evaluates the severity of psychopathology from 1 to 7, where 1 is 'normal' and 7 is 'among the most extremely ill patients' by the question Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?. | At follow up 12 months after intervention | 
| CGI-S (Clinical Global Impressions - Severity Scale) | A one-item clinician assessed measure which evaluates the severity of psychopathology from 1 to 7, where 1 is 'normal' and 7 is 'among the most extremely ill patients' by the question Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?. | At follow up 24 months after intervention | 
| CGI-S (Clinical Global Impressions - Severity Scale) | A one-item clinician assessed measure which evaluates the severity of psychopathology from 1 to 7, where 1 is 'normal' and 7 is 'among the most extremely ill patients' by the question Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?. | At follow up 36 months after intervention | 
| Blood pressure | systolic and diastolic, mmHg | change from inclusion to follow up 3 months after inclusion | 
| Blood pressure | systolic and diastolic, mmHg | At follow up 12 months after intervention | 
| Blood pressure | systolic and diastolic, mmHg | At follow up 24 months after intervention | 
| Blood pressure | systolic and diastolic, mmHg | At follow up 36 months after intervention | 
| Heart rate | Heart rate, beats per minute | change from inclusion to follow up 3 months after inclusion | 
| Heart rate | Heart rate, beats per minute | At follow up 12 months after intervention | 
| Heart rate | Heart rate, beats per minute | At follow up 24 months after intervention | 
| Heart rate | Heart rate, beats per minute | At follow up 36 months after intervention | 
| BMI (Body mass index) | Weight in kg divided by the square of height in m | change from inclusion to follow up 3 months after inclusion | 
| BMI (Body mass index) | Weight in kg divided by the square of height in m | At follow up 12 months after intervention | 
| BMI (Body mass index) | Weight in kg divided by the square of height in m | At follow up 24 months after intervention | 
| BMI (Body mass index) | Weight in kg divided by the square of height in m | At follow up 36 months after intervention | 
| Waist circumference | Waist circumference, cm | change from inclusion to follow up 3 months after inclusion | 
| Waist circumference | Waist circumference, cm | At follow up 12 months after intervention | 
| Waist circumference | Waist circumference, cm | At follow up 24 months after intervention | 
| Waist circumference | Waist circumference, cm | At follow up 36 months after intervention | 
| FBS (fasting blood sugar) | fasting blood sugar, mmol/l | Change from inclusion to follow up 3 months after inclusion | 
| FBS (fasting blood sugar) | fasting blood sugar, mmol/l | At follow up 12 months after intervention. | 
| FBS (fasting blood sugar) | fasting blood sugar, mmol/l | At follow up 24 months after intervention. | 
| FBS (fasting blood sugar) | fasting blood sugar, mmol/l | At follow up 36 months after intervention. | 
| HbA1c (Hemoglobin A1c) | Glycated hemoglobin, mmol/mol | change from inclusion to follow up 3 months after inclusion | 
| HbA1c (Hemoglobin A1c) | Glycated hemoglobin, mmol/mol | At follow up 12 months after intervention. | 
| HbA1c (Hemoglobin A1c) | Glycated hemoglobin, mmol/mol | At follow up 24 months after intervention. | 
| HbA1c (Hemoglobin A1c) | Glycated hemoglobin, mmol/mol | At follow up 36 months after intervention. | 
| Blood lipids | Total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, mmol/L | change from inclusion to follow up 3 months after inclusion | 
| Blood lipids | Total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, mmol/L | At follow up 12 months after intervention. | 
| Blood lipids | Total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, mmol/L | At follow up 24 months after intervention. | 
| Blood lipids | Total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, mmol/L | At follow up 36 months after intervention. | 
| CRP (C-reactive protein) | Measurement of inflammation and infection, mmol/L | change from inclusion to follow up 3 months after inclusion | 
| CRP (C-reactive protein) | Measurement of inflammation and infection, mmol/L | At follow up 12 months after intervention. | 
| CRP (C-reactive protein) | Measurement of inflammation and infection, mmol/L | At follow up 24 months after intervention. | 
| CRP (C-reactive protein) | Measurement of inflammation and infection, mmol/L | At follow up 36 months after intervention. | 
| Telomere length | telomere length in leukocytes | change from inclusion to follow up 3 months after inclusion | 
| Telomere length | telomere length in leukocytes | At follow up 12 months after intervention. | 
| Telomerase | Enzyme activity in blood | change from inclusion to follow up 3 months after inclusion | 
| Telomerase | Enzyme activity in blood | At follow up 12 months after intervention. | 
| WHODAS 2.0 (World health organization disability assessment schedule) | Self rated disability. Minimum value 0, maximum value 100, where higher values indicate more disability. | change from inclusion to follow up 3 months after inclusion | 
| WHODAS 2.0 (World health organization disability assessment schedule) | Self rated disability. Minimum value 0, maximum value 100, where higher values indicate more disability. | At follow up 12 months after intervention. | 
| WHODAS 2.0 (World health organization disability assessment schedule) | Self rated disability. Minimum value 0, maximum value 100, where higher values indicate more disability. | At follow up 24 months after intervention. | 
| WHODAS 2.0 (World health organization disability assessment schedule) | Self rated disability. Minimum value 0, maximum value 100, where higher values indicate more disability. | At follow up 36 months after intervention. | 
| EQ-5D-5L (EuroQol VAS) | Self-assessment instrument for describing and valuing health. Defines health in terms of five dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Also included is an overall health rating on a 0-100 hash-marked, vertical visual analogue scale (EQ-VAS). Assessment the scores from the descriptive component can be reported as a five digit number ranging from 11111 (full health) to 55555 (worst health). A number of methods exist for analysing these five digit profiles. However, frequently they are converted to a single utility index using country specific value sets. A higher index number indicates a poorer self-assessed health. | change from inclusion to follow up 3 months after inclusion | 
| EQ-5D-5L (EuroQol VAS) | Self-assessment instrument for describing and valuing health. Defines health in terms of five dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Also included is an overall health rating on a 0-100 hash-marked, vertical visual analogue scale (EQ-VAS). Assessment the scores from the descriptive component can be reported as a five digit number ranging from 11111 (full health) to 55555 (worst health). A number of methods exist for analysing these five digit profiles. However, frequently they are converted to a single utility index using country specific value sets. A higher index number indicates a poorer self-assessed health. | At follow up 12 months after intervention. | 
| EQ-5D-5L (EuroQol VAS) | Self-assessment instrument for describing and valuing health. Defines health in terms of five dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Also included is an overall health rating on a 0-100 hash-marked, vertical visual analogue scale (EQ-VAS). Assessment the scores from the descriptive component can be reported as a five digit number ranging from 11111 (full health) to 55555 (worst health). A number of methods exist for analysing these five digit profiles. However, frequently they are converted to a single utility index using country specific value sets. A higher index number indicates a poorer self-assessed health. | At follow up 24 months after intervention. | 
| EQ-5D-5L (EuroQol VAS) | Self-assessment instrument for describing and valuing health. Defines health in terms of five dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Also included is an overall health rating on a 0-100 hash-marked, vertical visual analogue scale (EQ-VAS). Assessment the scores from the descriptive component can be reported as a five digit number ranging from 11111 (full health) to 55555 (worst health). A number of methods exist for analysing these five digit profiles. However, frequently they are converted to a single utility index using country specific value sets. A higher index number indicates a poorer self-assessed health. | At follow up 36 months after intervention. | 
| SRH (Self-rated health) | SRH is typically measured as a single-item, the most common wording of which is In general, would you say your health is with the response items excellent, very good, good, fair, or poor. | change from inclusion to follow up 3 months after inclusion | 
| SRH (Self-rated health) | SRH is typically measured as a single-item, the most common wording of which is In general, would you say your health is with the response items excellent, very good, good, fair, or poor. | At follow up 12 months after intervention. | 
| SRH (Self-rated health) | SRH is typically measured as a single-item, the most common wording of which is In general, would you say your health is with the response items excellent, very good, good, fair, or poor. | At follow up 24 months after intervention. | 
| SRH (Self-rated health) | SRH is typically measured as a single-item, the most common wording of which is In general, would you say your health is with the response items excellent, very good, good, fair, or poor. | At follow up 36 months after intervention. | 
| BBQ (Brunnsviken Brief Quality of Life Questionnaire) | Self rated quality of life. Minimum value 0, maximum value 96, where higher values indicate higher quality of life satisfaction. | change from inclusion to follow up 3 months after inclusion | 
| BBQ (Brunnsviken Brief Quality of Life Questionnaire) | Self rated quality of life. Minimum value 0, maximum value 96, where higher values indicate higher quality of life satisfaction. | At follow up 12 months after intervention. | 
| BBQ (Brunnsviken Brief Quality of Life Questionnaire) | Self rated quality of life. Minimum value 0, maximum value 96, where higher values indicate higher quality of life satisfaction. | At follow up 24 months after intervention. | 
| BBQ (Brunnsviken Brief Quality of Life Questionnaire) | Self rated quality of life. Minimum value 0, maximum value 96, where higher values indicate higher quality of life satisfaction. | At follow up 36 months after intervention. | 
| Occupational level measured in % of work ability in medical certificate | Complete sick leave 0%, partial sick leave 25-75 %, completely able to work 100%. | change from inclusion to follow up 3 months after inclusion | 
| Occupational level measured in % of work ability in medical certificate | Complete sick leave 0%, partial sick leave 25-75 %, completely able to work 100%. | At follow up 12 months after intervention. | 
| Occupational level measured in % of work ability in medical certificate | Complete sick leave 0%, partial sick leave 25-75 %, completely able to work 100%. | At follow up 24 months after intervention. | 
| Occupational level measured in % of work ability in medical certificate | Complete sick leave 0%, partial sick leave 25-75 %, completely able to work 100%. | At follow up 36 months after intervention. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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physical exercise, physical activity