Buspirone in Parkinson's Disease

• Sponsor: University of Rochester (Other)
• Overall Status: Completed
• CT.gov ID: NCT02803749
• Collaborator: Michael J. Fox Foundation for Parkinson's Research (Other)
• Enrollment: 21
• Location: 1
• Arms: 2
• Duration (Months): 27.8
• Patients Per Site Per Month: 0.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Parkinson Disease; Anxiety	Drug: Buspirone; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Tolerability of Buspirone for the Treatment of Anxiety in Parkinson's Disease
• Study Start Date: Oct 1, 2016
• Actual Primary Completion Date: Jan 1, 2019
• Actual Study Completion Date: Jan 25, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Buspirone Flexible dosage buspirone (maximum dosage 30 mg twice daily) for 12 weeks.	Drug: Buspirone
Placebo Comparator: Placebo Flexible dosage placebo for 12 weeks.	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. The Number of Participants Who Fail to Complete the 12-week Study on Study Drug. [12 weeks]

Secondary Outcome Measures

1. 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.

2. 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.

3. 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."

4. 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.

5. 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.

6. 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."

7. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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 ≥

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Rochester Medical Center	Rochester	New York	United States	14618

Sponsors and Collaborators

• University of Rochester
• Michael J. Fox Foundation for Parkinson's Research

Investigators

• Principal Investigator: Irene Richard, MD, University of Rochester

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 27, 2016
• Informed Consent Form - Jun 9, 2016

More Information

Publications

None provided.

• Responsible Party: Irene Richard, Professor of Neurology, University of Rochester
• ClinicalTrials.gov Identifier: NCT02803749
• Other Study ID Numbers: 61141
• First Posted: Jun 17, 2016
• Last Update Posted: Jan 2, 2020
• Last Verified: Dec 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Parkinson Disease; Buspirone

Study Results

Participant Flow

Arm/Group Title	Buspirone	Placebo
Arm/Group Description	Flexible dosage buspirone (maximum dosage 30 mg twice daily) for 12 weeks. Buspirone	Flexible dosage placebo for 12 weeks. Placebo
Period Title: Overall Study
STARTED	17	4
COMPLETED	12	4
NOT COMPLETED	5	0

Baseline Characteristics

Arm/Group Title	Buspirone	Placebo	Total
Arm/Group Description	Flexible dosage buspirone (maximum dosage 30 mg twice daily) for 12 weeks. Buspirone	Flexible dosage placebo for 12 weeks. Placebo	Total of all reporting groups
Overall Participants	17	4	21
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.5 (9.8)	70.3 (10.6)	66.4 (9.9)
Sex: Female, Male (Count of Participants)
Female	4 23.5%	3 75%	7 33.3%
Male	13 76.5%	1 25%	14 66.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 5.9%	0 0%	1 4.8%
Not Hispanic or Latino	16 94.1%	4 100%	20 95.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	17 100%	4 100%	21 100%
Married participants (Count of Participants)
Count of Participants [Participants]	14 82.4%	4 100%	18 85.7%
Greater than high school education (Count of Participants)
Count of Participants [Participants]	14 82.4%	4 100%	18 85.7%
History of Depression (Count of Participants)
Count of Participants [Participants]	2 11.8%	1 25%	3 14.3%
Taking Antidepressant or Anxiolytic (Count of Participants)
Count of Participants [Participants]	15 88.2%	2 50%	17 81%
Hoehn and Yahr Stage (Count of Participants)
1	3 17.6%	0 0%	3 14.3%
2	11 64.7%	3 75%	14 66.7%
3	3 17.6%	0 0%	3 14.3%
4	0 0%	1 25%	1 4.8%
MDS-UPDRS (units on a scale) [Mean (Standard Deviation) ]
Total	59.6 (22.5)	67.5 (24.3)	61.1 (22.4)
nM-EDL	11.4 (5.2)	13 (5.2)	11.7 (5.1)
M-EDL	12.9 (7.6)	14.5 (7.5)	13.2 (7.4)
Motor	32.3 (15.3)	37.5 (11.7)	33.3 (14.5)
Motor Compications	3.0 (3.3)	3.3 (3.5)	3.1 (3.2)
Unified Dyskinesia Rating Scale (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	5.2 (7.3)	3.8 (5.2)	5.0 (6.9)
Parkinson Anxiety Scale (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	19.1 (3.9)	19.3 (5.1)	19.1 (4.0)
Hamilton Anxiety Scale (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	11.4 (4)	12.3 (2.9)	11.5 (3.7)
Hospital Anxiety and Depression Scale - Anxiety (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	8.2 (3.1)	6.8 (3.1)	7.9 (3.0)
Hospital Anxiety and Depression Scale - Depression (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	5.4 (3.1)	4.8 (2.6)	5.2 (3.0)
Montreal Cognitive Assessment (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	26.3 (2.3)	26.8 (2.1)	26.4 (2.2)
Started Taking Antidepressant or Anxiolytic during Study (Count of Participants)
Count of Participants [Participants]	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	The Number of Participants Who Fail to Complete the 12-week Study on Study Drug.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Buspirone	Placebo
Arm/Group Description	Flexible dosage buspirone (maximum dosage 30 mg twice daily) for 12 weeks. Buspirone	Flexible dosage placebo for 12 weeks. Placebo
Measure Participants	17	4
Count of Participants [Participants]	7 41.2%	0 0%

2. Secondary Outcome

Title	Mean Change in Hamilton Anxiety Rating Scale (HAM-A) From Baseline to 12 Weeks
Description	The HAM-A assess anxiety on 0-56 scale where a higher score represents a higher level of anxiety.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Buspirone	Placebo
Arm/Group Description	Flexible dosage buspirone (maximum dosage 30 mg twice daily) for 12 weeks. Buspirone	Flexible dosage placebo for 12 weeks. Placebo
Measure Participants	12	4
Mean (Standard Error) [score on a scale]	-4.21 (1.13)	-3.36 (1.97)

3. Secondary Outcome

Title	Number of Responders (>50% Reduction From Baseline or Reduction to ≤7 on HAM-A) at 12 Weeks
Description	The HAM-A assess anxiety on 0-56 scale where a higher score represents a higher level of anxiety.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Buspirone	Placebo
Arm/Group Description	Flexible dosage buspirone (maximum dosage 30 mg twice daily) for 12 weeks. Buspirone	Flexible dosage placebo for 12 weeks. Placebo
Measure Participants	12	4
Count of Participants [Participants]	9 52.9%	1 25%

4. Secondary Outcome

Title	Number of "Much Improved" or "Very Much Improved" on Patient Global Impressions-Improvement (PGI-I) at 12 Weeks
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Buspirone	Placebo
Arm/Group Description	Flexible dosage buspirone (maximum dosage 30 mg twice daily) for 12 weeks. Buspirone	Flexible dosage placebo for 12 weeks. Placebo
Measure Participants	12	4
Count of Participants [Participants]	3 17.6%	0 0%

5. Secondary Outcome

Title	Mean Change in Anxiety Using the Hospital Anxiety and Depression Scale (HADS)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Buspirone	Placebo
Arm/Group Description	Flexible dosage buspirone (maximum dosage 30 mg twice daily) for 12 weeks. Buspirone	Flexible dosage placebo for 12 weeks. Placebo
Measure Participants	12	4
Mean (Standard Error) [score on a scale]	-1.87 (0.98)	-0.89 (1.71)

6. Secondary Outcome

Title	Mean Change in Unified Dyskinesia Rating Scale (UDysRS) From Baseline to 12 Weeks
Description	The UDysRS assesses dyskinesias on a scale of 0-104 where a higher score represents more severe dyskinesias.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Buspirone	Placebo
Arm/Group Description	Flexible dosage buspirone (maximum dosage 30 mg twice daily) for 12 weeks. Buspirone	Flexible dosage placebo for 12 weeks. Placebo
Measure Participants	12	4
Mean (Standard Error) [score on a scale]	.72 (3.22)	7.78 (6.44)

7. Secondary Outcome

Title	Number of "Much Improved" or "Very Much Improved" on Clinical Global Impressions-Improvement (CGI-I) at 12 Weeks
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Buspirone	Placebo
Arm/Group Description	Flexible dosage buspirone (maximum dosage 30 mg twice daily) for 12 weeks. Buspirone	Flexible dosage placebo for 12 weeks. Placebo
Measure Participants	12	4
Count of Participants [Participants]	5 29.4%	2 50%

8. Secondary Outcome

Title	Mean Change in Hospital Anxiety and Depression Scale (HADS) - Depression From Baseline to 12 Weeks
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Buspirone	Placebo
Arm/Group Description	Flexible dosage buspirone (maximum dosage 30 mg twice daily) for 12 weeks. Buspirone	Flexible dosage placebo for 12 weeks. Placebo
Measure Participants	12	4
Mean (Standard Error) [units on a scale]	-.95 (.46)	.34 (.81)

Adverse Events

Time Frame	12 weeks
Arm/Group Title	Buspirone		Placebo
Arm/Group Description	Flexible dosage buspirone (maximum dosage 30 mg twice daily) for 12 weeks. Buspirone		Flexible dosage placebo for 12 weeks. Placebo
All Cause Mortality
	Buspirone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/4 (0%)
Serious Adverse Events
	Buspirone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Buspirone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/17 (29.4%)		3/4 (75%)
Eye disorders
Vision Changes	0/17 (0%)		1/4 (25%)
Gastrointestinal disorders
Gastritis/Duodenitis	1/17 (5.9%)		0/4 (0%)
Gastrointestinal Illness	1/17 (5.9%)		0/4 (0%)
General disorders
Increased freezing of gait	5/17 (29.4%)		0/4 (0%)
tremor	3/17 (17.6%)		0/4 (0%)
sleep difficulties	2/17 (11.8%)		2/4 (50%)
dizziness	2/17 (11.8%)		0/4 (0%)
increased fatigue	2/17 (11.8%)		0/4 (0%)
increased tremor	1/17 (5.9%)		3/4 (75%)
balance impairment	1/17 (5.9%)		2/4 (50%)
increased peripheral edema	1/17 (5.9%)		1/4 (25%)
Gait Difficulties	0/17 (0%)		1/4 (25%)
Vertigo	0/17 (0%)		1/4 (25%)
Weakness	0/17 (0%)		1/4 (25%)
Bradycardia	1/17 (5.9%)		0/4 (0%)
Constipation	1/17 (5.9%)		0/4 (0%)
Dysphagia	1/17 (5.9%)		0/4 (0%)
Fuzziness	1/17 (5.9%)		0/4 (0%)
Hand Cramps	1/17 (5.9%)		0/4 (0%)
Headache	1/17 (5.9%)		0/4 (0%)
Increased agitation	1/17 (5.9%)		0/4 (0%)
Increased appetite	1/17 (5.9%)		0/4 (0%)
Increased balance impairment	1/17 (5.9%)		0/4 (0%)
Increased dystonia	1/17 (5.9%)		0/4 (0%)
Increased irritability	1/17 (5.9%)		0/4 (0%)
Increased Knee pain	1/17 (5.9%)		0/4 (0%)
Increased OFF time	1/17 (5.9%)		0/4 (0%)
increased pain secondary to lipomas	1/17 (5.9%)		0/4 (0%)
insomnia	1/17 (5.9%)		0/4 (0%)
joint stiffness	1/17 (5.9%)		0/4 (0%)
Left shoulder/neck pain	1/17 (5.9%)		0/4 (0%)
leg pain	1/17 (5.9%)		0/4 (0%)
nasal congestion	1/17 (5.9%)		0/4 (0%)
numbness	1/17 (5.9%)		0/4 (0%)
Injury, poisoning and procedural complications
Fall	0/17 (0%)		1/4 (25%)
Respiratory, thoracic and mediastinal disorders
Respiratory infection	1/17 (5.9%)		0/4 (0%)
Skin and subcutaneous tissue disorders
Rash	1/17 (5.9%)		1/4 (25%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.