Major Depressive Disorder
Conditions
Keywords
depressed, older adults, Major Depressive Disorder, Tai-Chi, geriatric
Brief summary
The purpose of this study is to evaluate the effects after up to 1 year of supervised weekly Tai-Chi-Chi versus Health Education and Wellness classes on reduction of depressive symptoms and improvement in resilience, health functioning, quality of life, cognition, sleep, fMRI neural correlates of working memory, and brain structure.
Detailed description
The proposed randomized trial aims to investigate neural mechanisms of brain connectivity when comparing response to TCC to health and wellness education classes using fMRI biomarkers of emotional regulation and cognition. Control group will include health wellness education programs (HEW) that will help to control for the non-specific social support factors. Primary outcomes include measures of depressive symptom severity. Secondary outcomes include cognition, resilience, health functioning, quality of life. Maintenance of response and relapse of major depression will be determined during 6 month (and 12 month follow-up if MRI eligible). Functional magnetic resonance imaging (fMRI) correlates of emotional processing and connectivity in related functional networks. Neural correlates of working memory, and brain structure will be examined in ½ of the sample. The researchers will investigate whether variations in emotional regulation will moderate or predict emotional and functional improvement linked to TCC. The investigators will recruit 220 older adults with depressive symptoms who have been on a stable form of treatment for at least 4 months, who will be randomly assigned to 12 weeks of: 1.Ta-Chi-Chih (TCC) class; or 2. Health/Wellness Education Program (HEW); all for 120 minutes per week. All subjects will receive comprehensive evaluations of mood, mental and physical health, and cognition at baseline, 12 weeks, and 6 months. Changes over time in measures of depressive symptoms, resilience, quality of life, and cognition will be assessed in random regression models. The investigators anticipate that greater clinical improvement in mood and cognition will in the TCC group compared to the HEW. The investigators also expect clinical improvement to correlate with the change in the activation in the right ventrolateral prefrontal cortex (VLPFC) and amygdala in an affect labeling task, and working memory-related activation of dorsolateral prefrontal cortex (DLPFC), and change in functional connectivity in brain network activity. This is the first randomized trial of response to TCC that integrates the use of fMRI biomarkers of response to guide the development of treatment and preventive approaches in geriatric depression.
Interventions
BEHAVIORALTai-Chi-Chih (TCC)
BEHAVIORALHealth Education and Wellness Classes (HEW)
Sponsors
University of California, Los Angeles
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A 24-item Hamilton Rating Scale for Depression (HAMD) score greater than 14 consistent with moderate-severe depression. * Mini-Mental State Exam (MMSE) score greater than 24. * Sufficient English proficiency and 8th grade or higher reading level as determined by the word reading subtest of the Wide Range Achievement Test-IV. * Capacity to provide informed consent. * A stable form of treatment for at least 4 months.
Exclusion criteria
* Any current or past psychiatric disorders, or recent unstable medical or neurological disorders * Any disabilities preventing their participation in Tai-Chi Chih exercise (e.g. severe visual or hearing impairment) * Insufficient English proficiency * Diagnosis of dementia * Mini Mental Health Examination score of 24 and below * Effective antidepressant, psychotropic medications, or effective therapy * Participation in a psychotherapy that involves cognitive training * Do not meet criteria for moderate-severe depression with a 24-item Hamilton Rating Scale for Depression (HAMD) score less than 14
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hamilton Depression Rating Scale (HDRS) Scores | Measured at baseline and 3 months | Clinician administered scale measures severity of depressive symptoms. This measure includes 24 items. Response options vary item to item and include the following ranges: \[0-2\], \[0-3\], and \[0-4\]. A score of 0 suggests absence of symptoms and/or difficulties and higher scores represent more severe difficulties. Possible overall score range \[0-74\], higher scores representing more severe difficulties. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Delayed Recall Cognitive Domain Scores | Measured at baseline and 3 months | Neuropsychological battery of tests which included the following domains: Delayed Recall (CVLT-II \[Long-Delay Free Recall\], Rey-Osterrieth Complex Figure Test \[30-minute Delayed Recall\]) Raw scores were transformed to z-scores (with a mean of 0 and standard deviation of 1) for each test score of interest across all participants. Thus the sample mean (across both arms) is zero for each test score. These z-scores were then averaged within each neuropsychological domain to produce composite scores. Higher scores are indicative of better performance. |
| Change in Attention/Executive Function Cognitive Domain Scores | Measured at baseline and 3 months | Neuropsychological battery of tests which included the following domains: Attention/Executive Function (Trail Making Test A and B, Stroop Interference \[Golden version\]) Raw scores were transformed to z-scores (with a mean of 0 and standard deviation of 1) for each test score of interest across all participants. Thus the sample mean (across both arms) is zero for each test score. These z-scores were then averaged within each neuropsychological domain to produce composite scores. Higher scores are indicative of better performance. |
| Change in Language Cognitive Domain Scores | Measured at baseline and 3 months | Neuropsychological battery of tests which included the following domains: Language (Controlled Oral Word Association test \[FAS\], Animal Fluency, and Boston Naming Test) Raw scores were transformed to z-scores (with a mean of 0 and standard deviation of 1) for each test score of interest across all participants. Thus the sample mean (across both arms) is zero for each test score. These z-scores were then averaged within each neuropsychological domain to produce composite scores. Higher scores are indicative of better performance. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | Measured at 3 months | The UKU (Udvalg for Kliniske Undersogelser) Side Effect Rating Scale organizes symptoms into 4 categories (i.e., Psychic, Neurologic, Autonomic, Other) containing 8-19 symptoms each. Each symptom receives a score for degree and causal relationship. Degree is scored between 0-3 with higher scores being more severe. Causal relationship is scored as improbable, possible, or probable. |
Countries
United States
Participant flow
Pre-assignment details
220 participants were enrolled after providing consent and completing the screen visit. 178 participants completed baseline procedures and were randomized to either group.
Participants by arm
| Arm | Count |
|---|---|
| Tai-Chi Chih Classes Participants will engage in 12 weekly 60 minute Tai-Chi-Chih classes.
Tai-Chi-Chih (TCC) | 89 |
| Health Education and Wellness Classes Participants will engage in 12 weekly 60 minute Health Education and Wellness classes.
Health Education and Wellness Classes (HEW) | 89 |
| Total | 178 |
Baseline characteristics
| Characteristic | Health Education and Wellness Classes | Total | Tai-Chi Chih Classes |
|---|---|---|---|
| Age, Continuous | 69.4 years STANDARD_DEVIATION 6.2 | 69.3 years STANDARD_DEVIATION 6.6 | 69.2 years STANDARD_DEVIATION 6.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 6 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 85 Participants | 168 Participants | 83 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 4 Participants | 3 Participants |
| Hamilton Depression Rating Scale | 19.3 units on a scale STANDARD_DEVIATION 3.9 | 19.15 units on a scale STANDARD_DEVIATION 3.91 | 19.0 units on a scale STANDARD_DEVIATION 4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 8 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 13 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) White | 77 Participants | 153 Participants | 76 Participants |
| Region of Enrollment United States | 89 participants | 178 participants | 89 participants |
| Sex: Female, Male Female | 67 Participants | 129 Participants | 62 Participants |
| Sex: Female, Male Male | 22 Participants | 49 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 89 | 0 / 89 |
| other Total, other adverse events | 4 / 89 | 3 / 89 |
| serious Total, serious adverse events | 0 / 89 | 0 / 89 |
Outcome results
Primary
Change in Hamilton Depression Rating Scale (HDRS) Scores
Clinician administered scale measures severity of depressive symptoms. This measure includes 24 items. Response options vary item to item and include the following ranges: \[0-2\], \[0-3\], and \[0-4\]. A score of 0 suggests absence of symptoms and/or difficulties and higher scores represent more severe difficulties. Possible overall score range \[0-74\], higher scores representing more severe difficulties.
Time frame: Measured at baseline and 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tai-Chi Chih Classes | Change in Hamilton Depression Rating Scale (HDRS) Scores | -9.27 units on a scale | Standard Deviation 5.29 |
| Health Education and Wellness Classes | Change in Hamilton Depression Rating Scale (HDRS) Scores | -9.40 units on a scale | Standard Deviation 5.35 |
p-value: 0.3Mixed Models Analysis
Secondary
Change in Attention/Executive Function Cognitive Domain Scores
Neuropsychological battery of tests which included the following domains: Attention/Executive Function (Trail Making Test A and B, Stroop Interference \[Golden version\]) Raw scores were transformed to z-scores (with a mean of 0 and standard deviation of 1) for each test score of interest across all participants. Thus the sample mean (across both arms) is zero for each test score. These z-scores were then averaged within each neuropsychological domain to produce composite scores. Higher scores are indicative of better performance.
Time frame: Measured at baseline and 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tai-Chi Chih Classes | Change in Attention/Executive Function Cognitive Domain Scores | -0.04 z-score | Standard Deviation 0.61 |
| Health Education and Wellness Classes | Change in Attention/Executive Function Cognitive Domain Scores | 0.03 z-score | Standard Deviation 0.53 |
p-value: 0.5Mixed Models Analysis
Secondary
Change in Delayed Recall Cognitive Domain Scores
Neuropsychological battery of tests which included the following domains: Delayed Recall (CVLT-II \[Long-Delay Free Recall\], Rey-Osterrieth Complex Figure Test \[30-minute Delayed Recall\]) Raw scores were transformed to z-scores (with a mean of 0 and standard deviation of 1) for each test score of interest across all participants. Thus the sample mean (across both arms) is zero for each test score. These z-scores were then averaged within each neuropsychological domain to produce composite scores. Higher scores are indicative of better performance.
Time frame: Measured at baseline and 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tai-Chi Chih Classes | Change in Delayed Recall Cognitive Domain Scores | -0.15 z-score | Standard Deviation 0.57 |
| Health Education and Wellness Classes | Change in Delayed Recall Cognitive Domain Scores | -0.002 z-score | Standard Deviation 0.61 |
p-value: 0.2Mixed Models Analysis
Secondary
Change in Language Cognitive Domain Scores
Neuropsychological battery of tests which included the following domains: Language (Controlled Oral Word Association test \[FAS\], Animal Fluency, and Boston Naming Test) Raw scores were transformed to z-scores (with a mean of 0 and standard deviation of 1) for each test score of interest across all participants. Thus the sample mean (across both arms) is zero for each test score. These z-scores were then averaged within each neuropsychological domain to produce composite scores. Higher scores are indicative of better performance.
Time frame: Measured at baseline and 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tai-Chi Chih Classes | Change in Language Cognitive Domain Scores | 0.03 z-score | Standard Deviation 0.4 |
| Health Education and Wellness Classes | Change in Language Cognitive Domain Scores | -0.12 z-score | Standard Deviation 0.46 |
p-value: 0.09Mixed Models Analysis
Other Pre-specified
Number of Participants With Adverse Events
The UKU (Udvalg for Kliniske Undersogelser) Side Effect Rating Scale organizes symptoms into 4 categories (i.e., Psychic, Neurologic, Autonomic, Other) containing 8-19 symptoms each. Each symptom receives a score for degree and causal relationship. Degree is scored between 0-3 with higher scores being more severe. Causal relationship is scored as improbable, possible, or probable.
Time frame: Measured at 3 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tai-Chi Chih Classes | Number of Participants With Adverse Events | 4 Participants |
| Health Education and Wellness Classes | Number of Participants With Adverse Events | 3 Participants |