Anxiety, Parkinson Disease
Conditions
Brief summary
Anxiety is highly prevalent in Parkinson's disease and negatively impacts quality of life yet it frequently remains untreated and there have been no clinical trials dedicated to evaluating the pharmacological treatment of anxiety in Parkinson's disease. Buspirone is effective for the treatment of generalized anxiety disorder in the general and elderly population. It is not known if it is effective for the treatment of anxiety in Parkinson's disease. This is a single-center, placebo-controlled, double-blind design with participants randomized with a 4:1 allocation ratio to flexible dosage buspirone (maximum dosage 30 mg twice daily) or placebo for 12 weeks.
Interventions
DRUGBuspirone
DRUGPlacebo
Sponsors
Michael J. Fox Foundation for Parkinson's Research
University of Rochester
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of idiopathic PD by UK Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria * Significant anxiety as determined by the self-rated Parkinson Anxiety Scale (score ≥ 14) * Able to provide written informed consent * At least 18 years of age
Exclusion criteria
* Diagnosis of atypical or secondary parkinsonism * Concomitant treatment with an MAO inhibitor within the 14 days prior to screening visit * Significant renal or hepatic impairment * Significant cognitive impairment defined as MOCA score \< 23 * On-going depression with suicidal or homicidal ideation and concern for patient safety based on clinical determination by the investigator * Allergy or intolerance to study drug, matching placebo, or their formulations * History of prior exposure to study drug * Lactating or pregnant woman * Concomitant treatment with a disallowed medication (detailed in section 6.2) * Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements * Concomitant treatment with an anxiolytic or antidepressant will be allowed however potential participants who had dosage changes in the 30 days prior to the screening visit will be excluded * Use of an investigational drug within 30 days prior to screening visit * Any medical or psychiatric comorbidity that, in the opinion of the investigator, would compromise study participation * Dysphagia defined as a score of ≥ 2 on MDS-UPDRS Item 2.3 Chewing and Swallowing
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Number of Participants Who Fail to Complete the 12-week Study on Study Drug. | 12 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Hamilton Anxiety Rating Scale (HAM-A) From Baseline to 12 Weeks | 12 weeks | The HAM-A assess anxiety on 0-56 scale where a higher score represents a higher level of anxiety. |
| Number of Responders (>50% Reduction From Baseline or Reduction to ≤7 on HAM-A) at 12 Weeks | 12 weeks | The HAM-A assess anxiety on 0-56 scale where a higher score represents a higher level of anxiety. |
| Mean Change in Anxiety Using the Hospital Anxiety and Depression Scale (HADS) | baseline to 12 weeks | The HADS assesses anxiety on a scale of 0-21 and depression on a scale of 0-21 with higher scores indicating higher levels of anxiety and depression respectively. |
| Number of Much Improved or Very Much Improved on Patient Global Impressions-Improvement (PGI-I) at 12 Weeks | 12 weeks | The PGI-I assesses patient global impression of improvement on a 7-point scale where 1 = very much improved and 7 = very much worse. |
| Number of Much Improved or Very Much Improved on Clinical Global Impressions-Improvement (CGI-I) at 12 Weeks | 12 weeks | The CGI-I assesses clinician global impression of improvement on a 7-point scale where 1 = very much improved and 7 = very much worse. |
| Mean Change in Hospital Anxiety and Depression Scale (HADS) - Depression From Baseline to 12 Weeks | 12 weeks | The HADS assesses anxiety on a scale of 0-21 and depression on a scale of 0-21 with higher scores indicating higher levels of anxiety and depression respectively. |
| Mean Change in Unified Dyskinesia Rating Scale (UDysRS) From Baseline to 12 Weeks | 12 weeks | The UDysRS assesses dyskinesias on a scale of 0-104 where a higher score represents more severe dyskinesias. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Buspirone Flexible dosage buspirone (maximum dosage 30 mg twice daily) for 12 weeks.
Buspirone | 17 |
| Placebo Flexible dosage placebo for 12 weeks.
Placebo | 4 |
| Total | 21 |
Baseline characteristics
| Characteristic | Buspirone | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 65.5 years STANDARD_DEVIATION 9.8 | 66.4 years STANDARD_DEVIATION 9.9 | 70.3 years STANDARD_DEVIATION 10.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 20 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Greater than high school education | 14 Participants | 18 Participants | 4 Participants |
| Hamilton Anxiety Scale | 11.4 units on a scale STANDARD_DEVIATION 4 | 11.5 units on a scale STANDARD_DEVIATION 3.7 | 12.3 units on a scale STANDARD_DEVIATION 2.9 |
| History of Depression | 2 Participants | 3 Participants | 1 Participants |
| Hoehn and Yahr Stage 1 | 3 Participants | 3 Participants | 0 Participants |
| Hoehn and Yahr Stage 2 | 11 Participants | 14 Participants | 3 Participants |
| Hoehn and Yahr Stage 3 | 3 Participants | 3 Participants | 0 Participants |
| Hoehn and Yahr Stage 4 | 0 Participants | 1 Participants | 1 Participants |
| Hospital Anxiety and Depression Scale - Anxiety | 8.2 units on a scale STANDARD_DEVIATION 3.1 | 7.9 units on a scale STANDARD_DEVIATION 3 | 6.8 units on a scale STANDARD_DEVIATION 3.1 |
| Hospital Anxiety and Depression Scale - Depression | 5.4 units on a scale STANDARD_DEVIATION 3.1 | 5.2 units on a scale STANDARD_DEVIATION 3 | 4.8 units on a scale STANDARD_DEVIATION 2.6 |
| Married participants | 14 Participants | 18 Participants | 4 Participants |
| MDS-UPDRS M-EDL | 12.9 units on a scale STANDARD_DEVIATION 7.6 | 13.2 units on a scale STANDARD_DEVIATION 7.4 | 14.5 units on a scale STANDARD_DEVIATION 7.5 |
| MDS-UPDRS Motor | 32.3 units on a scale STANDARD_DEVIATION 15.3 | 33.3 units on a scale STANDARD_DEVIATION 14.5 | 37.5 units on a scale STANDARD_DEVIATION 11.7 |
| MDS-UPDRS Motor Compications | 3.0 units on a scale STANDARD_DEVIATION 3.3 | 3.1 units on a scale STANDARD_DEVIATION 3.2 | 3.3 units on a scale STANDARD_DEVIATION 3.5 |
| MDS-UPDRS nM-EDL | 11.4 units on a scale STANDARD_DEVIATION 5.2 | 11.7 units on a scale STANDARD_DEVIATION 5.1 | 13 units on a scale STANDARD_DEVIATION 5.2 |
| MDS-UPDRS Total | 59.6 units on a scale STANDARD_DEVIATION 22.5 | 61.1 units on a scale STANDARD_DEVIATION 22.4 | 67.5 units on a scale STANDARD_DEVIATION 24.3 |
| Montreal Cognitive Assessment | 26.3 units on a scale STANDARD_DEVIATION 2.3 | 26.4 units on a scale STANDARD_DEVIATION 2.2 | 26.8 units on a scale STANDARD_DEVIATION 2.1 |
| Parkinson Anxiety Scale | 19.1 units on a scale STANDARD_DEVIATION 3.9 | 19.1 units on a scale STANDARD_DEVIATION 4 | 19.3 units on a scale STANDARD_DEVIATION 5.1 |
| Region of Enrollment United States | 17 participants | 21 participants | 4 participants |
| Sex: Female, Male Female | 4 Participants | 7 Participants | 3 Participants |
| Sex: Female, Male Male | 13 Participants | 14 Participants | 1 Participants |
| Started Taking Antidepressant or Anxiolytic during Study | 0 Participants | 0 Participants | 0 Participants |
| Taking Antidepressant or Anxiolytic | 15 Participants | 17 Participants | 2 Participants |
| Unified Dyskinesia Rating Scale | 5.2 units on a scale STANDARD_DEVIATION 7.3 | 5.0 units on a scale STANDARD_DEVIATION 6.9 | 3.8 units on a scale STANDARD_DEVIATION 5.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 4 |
| other Total, other adverse events | 5 / 17 | 3 / 4 |
| serious Total, serious adverse events | 0 / 17 | 0 / 4 |
Outcome results
Primary
The Number of Participants Who Fail to Complete the 12-week Study on Study Drug.
Time frame: 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Buspirone | The Number of Participants Who Fail to Complete the 12-week Study on Study Drug. | 7 Participants |
| Placebo | The Number of Participants Who Fail to Complete the 12-week Study on Study Drug. | 0 Participants |
Secondary
Mean Change in Anxiety Using the Hospital Anxiety and Depression Scale (HADS)
The HADS assesses anxiety on a scale of 0-21 and depression on a scale of 0-21 with higher scores indicating higher levels of anxiety and depression respectively.
Time frame: baseline to 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | Mean Change in Anxiety Using the Hospital Anxiety and Depression Scale (HADS) | -1.87 score on a scale | Standard Error 0.98 |
| Placebo | Mean Change in Anxiety Using the Hospital Anxiety and Depression Scale (HADS) | -0.89 score on a scale | Standard Error 1.71 |
Secondary
Mean Change in Hamilton Anxiety Rating Scale (HAM-A) From Baseline to 12 Weeks
The HAM-A assess anxiety on 0-56 scale where a higher score represents a higher level of anxiety.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | Mean Change in Hamilton Anxiety Rating Scale (HAM-A) From Baseline to 12 Weeks | -4.21 score on a scale | Standard Error 1.13 |
| Placebo | Mean Change in Hamilton Anxiety Rating Scale (HAM-A) From Baseline to 12 Weeks | -3.36 score on a scale | Standard Error 1.97 |
Secondary
Mean Change in Hospital Anxiety and Depression Scale (HADS) - Depression From Baseline to 12 Weeks
The HADS assesses anxiety on a scale of 0-21 and depression on a scale of 0-21 with higher scores indicating higher levels of anxiety and depression respectively.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | Mean Change in Hospital Anxiety and Depression Scale (HADS) - Depression From Baseline to 12 Weeks | -.95 units on a scale | Standard Error 0.46 |
| Placebo | Mean Change in Hospital Anxiety and Depression Scale (HADS) - Depression From Baseline to 12 Weeks | .34 units on a scale | Standard Error 0.81 |
Secondary
Mean Change in Unified Dyskinesia Rating Scale (UDysRS) From Baseline to 12 Weeks
The UDysRS assesses dyskinesias on a scale of 0-104 where a higher score represents more severe dyskinesias.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | Mean Change in Unified Dyskinesia Rating Scale (UDysRS) From Baseline to 12 Weeks | .72 score on a scale | Standard Error 3.22 |
| Placebo | Mean Change in Unified Dyskinesia Rating Scale (UDysRS) From Baseline to 12 Weeks | 7.78 score on a scale | Standard Error 6.44 |
Secondary
Number of Much Improved or Very Much Improved on Clinical Global Impressions-Improvement (CGI-I) at 12 Weeks
The CGI-I assesses clinician global impression of improvement on a 7-point scale where 1 = very much improved and 7 = very much worse.
Time frame: 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Buspirone | Number of Much Improved or Very Much Improved on Clinical Global Impressions-Improvement (CGI-I) at 12 Weeks | 5 Participants |
| Placebo | Number of Much Improved or Very Much Improved on Clinical Global Impressions-Improvement (CGI-I) at 12 Weeks | 2 Participants |
Secondary
Number of Much Improved or Very Much Improved on Patient Global Impressions-Improvement (PGI-I) at 12 Weeks
The PGI-I assesses patient global impression of improvement on a 7-point scale where 1 = very much improved and 7 = very much worse.
Time frame: 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Buspirone | Number of Much Improved or Very Much Improved on Patient Global Impressions-Improvement (PGI-I) at 12 Weeks | 3 Participants |
| Placebo | Number of Much Improved or Very Much Improved on Patient Global Impressions-Improvement (PGI-I) at 12 Weeks | 0 Participants |
Secondary
Number of Responders (>50% Reduction From Baseline or Reduction to ≤7 on HAM-A) at 12 Weeks
The HAM-A assess anxiety on 0-56 scale where a higher score represents a higher level of anxiety.
Time frame: 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Buspirone | Number of Responders (>50% Reduction From Baseline or Reduction to ≤7 on HAM-A) at 12 Weeks | 9 Participants |
| Placebo | Number of Responders (>50% Reduction From Baseline or Reduction to ≤7 on HAM-A) at 12 Weeks | 1 Participants |