Parkinson Disease
Conditions
Keywords
terazosin
Brief summary
The TZ-PD trial will be a 1:1 (active:placebo) randomized, double-blind, placebo-controlled Phase II trial to evaluate the safety and tolerability of terazosin for the treatment of PD.
Detailed description
This will be a single center, randomized, double-blind, controlled, pilot study to assess the safety and tolerability of terazosin (TZ) at a dose of 5 milligrams (MG) daily for patients with PD. The primary goal of this study is to assess the safety and tolerability of TZ in patients with PD. This is a pilot study and is not powered to assess efficacy of this medication. Our hope is that this study will guide future studies of this (and similar) medications for the disease modification of PD. This study is also aimed to learn more about how patients with produce and use energy and if TZ can help to reverse energy deficits that appear in PD.
Interventions
DRUGTerazosin 5 MG
5 milligrams by mouth daily at bedtime
DRUGPlacebo oral capsule
1 capsule by mouth daily at bedtime
Sponsors
University of Iowa
Jordan Schultz
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Men or women aged 40 and older with the diagnosis of idiopathic PD per UK Brain Bank criteria * Hoehn-Yahr Stage I-III, on stable dopaminergic treatment regimen for ≥4 weeks prior to baseline.
Exclusion criteria
* Subjects unwilling or unable to give informed consent * Secondary parkinsonism (e.g., drug induced) * Parkinson-plus syndromes * History of brain surgery for PD such as deep brain stimulation * No confounding acute or unstable medical, psychiatric, orthopedic condition. Subjects who have hypertension, diabetes mellitus, depression, or other common age-related illness will be included if their disease under control with stable treatment regimen for at least 30 days. * Neurogenic orthostatic hypotension defined as symptomatic decrease in BP \> 20mmHg systolic or \> 10mmHg diastolic and HR increase \< 20bpm on supine to sitting or standing. * Clinically significant traumatic brain injury or post-traumatic stress disorder * Presence of other known medical or psychiatric comorbidity that in the investigator's opinion would compromise participation in the study * Presence of dementia per Movement Disorder Society Level I criteria * Major depression, bipolar affective disorder, or other mental health disorders that are sufficiently severe to increase adverse event risk or impact neuropathy assessment in the opinion of the responsible site principal investigator. * Subjects with clinically significant depression as determined by a Beck Depression Inventory score greater than 21 at the screening visit * Current suicidal ideation within one year prior to the baseline visit as evidenced by answering yes to Questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale (C-SSRS) * If the participant has a Beck Anxiety Score greater than 22 at the initial screening visit. * History of exposure to typical or atypical antipsychotics or other dopamine blocking agents within 6 months prior to the baseline visit * Use of investigational drugs within 30 days before screening * Subjects have to be on a stable regimen of central nervous system acting medications (benzodiazepines, antidepressants, hypnotics) for 30 days prior to the baseline visit * Use of doxazosin, alfuzosin, prazosin, or tamsulosin * For female participant, pregnancy, or plans for child-bearing during study period * Participant is restricted from traveling to and from the study site
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Intervention-related Adverse Events Between Treatment Arms | 12 weeks | All patient-reported adverse events will be determine to be related to the study intervention by the site investigator. |
| Incidence of Falls Between Treatment Arms | 12 weeks | The number of participants in each group who report a fall, as determined by the site investigator, will be reported. |
| Frequency of Drop-out From Study/Discontinuation of Study Intervention for Any Reason | 12 weeks | The number of participants in each group who drop out of the study for any reason will be compared. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Assess the Mean Change in Blood Pressure | At Baseline, 2 weeks, 6 weeks, and 12 weeks | Mean change in sitting systolic blood pressure and diastolic blood pressure from baseline reading at 2 weeks, 6 weeks, and 12 weeks. A negative number indicates a decrease in blood pressure while a positive number indicates an increase in blood pressure. |
| Number of Participants With Intolerable Side Effects | 12 weeks | How many participants discontinued study as a result of intolerable adverse events that were deemed to be medication-related. |
| Participants Demonstrating Non-Compliance | At 2 weeks, 6 weeks and 12 weeks | All participants will be asked to bring their study intervention bottles to their 6 week visit and their 12 week visit so the Investigational Drug Pharmacy can count remaining pills and assess compliance based on dispensing history. A participant will be considered non-compliant if they had more than 5 missed doses during the course of the study. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Terazosin administered 5 mg once daily p.o. for 12 weeks
Terazosin 5 MG: 5 milligrams by mouth daily at bedtime | 8 |
| Placebo Placebo administered once daily p.o. for 12 weeks
Placebo oral capsule: 1 capsule by mouth daily at bedtime | 5 |
| Total | 13 |
Baseline characteristics
| Characteristic | Placebo | Total | Active |
|---|---|---|---|
| Age, Continuous | 68.8 years STANDARD_DEVIATION 6.6 | 66.4 years STANDARD_DEVIATION 6.3 | 64.8 years STANDARD_DEVIATION 6.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 13 Participants | 8 Participants |
| Sex: Female, Male Female | 2 Participants | 7 Participants | 5 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 5 |
| other Total, other adverse events | 8 / 8 | 2 / 5 |
| serious Total, serious adverse events | 0 / 8 | 0 / 5 |
Outcome results
Primary
Frequency of Drop-out From Study/Discontinuation of Study Intervention for Any Reason
The number of participants in each group who drop out of the study for any reason will be compared.
Time frame: 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active | Frequency of Drop-out From Study/Discontinuation of Study Intervention for Any Reason | 3 Participants |
| Placebo | Frequency of Drop-out From Study/Discontinuation of Study Intervention for Any Reason | 0 Participants |
Primary
Incidence of Falls Between Treatment Arms
The number of participants in each group who report a fall, as determined by the site investigator, will be reported.
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active | Incidence of Falls Between Treatment Arms | 0 Event |
| Placebo | Incidence of Falls Between Treatment Arms | 0 Event |
Primary
Incidence of Intervention-related Adverse Events Between Treatment Arms
All patient-reported adverse events will be determine to be related to the study intervention by the site investigator.
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active | Incidence of Intervention-related Adverse Events Between Treatment Arms | 11 Event |
| Placebo | Incidence of Intervention-related Adverse Events Between Treatment Arms | 4 Event |
Secondary
Number of Participants With Intolerable Side Effects
How many participants discontinued study as a result of intolerable adverse events that were deemed to be medication-related.
Time frame: 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active | Number of Participants With Intolerable Side Effects | 3 Participants |
| Placebo | Number of Participants With Intolerable Side Effects | 0 Participants |
Secondary
Participants Demonstrating Non-Compliance
All participants will be asked to bring their study intervention bottles to their 6 week visit and their 12 week visit so the Investigational Drug Pharmacy can count remaining pills and assess compliance based on dispensing history. A participant will be considered non-compliant if they had more than 5 missed doses during the course of the study.
Time frame: At 2 weeks, 6 weeks and 12 weeks
Population: Number of participants analyzed changes at different time points due to participant drop-out
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Active | Participants Demonstrating Non-Compliance | Non-compliance at 12 weeks | 0 Participants |
| Active | Participants Demonstrating Non-Compliance | Non-compliance at 2 weeks | 0 Participants |
| Active | Participants Demonstrating Non-Compliance | Non-compliance at 6 weeks | 0 Participants |
| Placebo | Participants Demonstrating Non-Compliance | Non-compliance at 6 weeks | 0 Participants |
| Placebo | Participants Demonstrating Non-Compliance | Non-compliance at 12 weeks | 0 Participants |
| Placebo | Participants Demonstrating Non-Compliance | Non-compliance at 2 weeks | 0 Participants |
Secondary
To Assess the Mean Change in Blood Pressure
Mean change in sitting systolic blood pressure and diastolic blood pressure from baseline reading at 2 weeks, 6 weeks, and 12 weeks. A negative number indicates a decrease in blood pressure while a positive number indicates an increase in blood pressure.
Time frame: At Baseline, 2 weeks, 6 weeks, and 12 weeks
Population: Change in Systolic BP at 2 weeks, 6 weeks, and 12 weeks Change in Diastolic BP at 2 weeks, 6 weeks, and 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active | To Assess the Mean Change in Blood Pressure | Systolic at 2 weeks | -5.29 mmHg | Standard Deviation 12.6 |
| Active | To Assess the Mean Change in Blood Pressure | Systolic at 6 weeks | -15.05 mmHg | Standard Deviation 8.21 |
| Active | To Assess the Mean Change in Blood Pressure | Systolic at 12 weeks | -11.0 mmHg | Standard Deviation 16.1 |
| Active | To Assess the Mean Change in Blood Pressure | Diastolic at 2 weeks | -2.00 mmHg | Standard Deviation 5.54 |
| Active | To Assess the Mean Change in Blood Pressure | Diastolic at 6 weeks | -5.29 mmHg | Standard Deviation 4.54 |
| Active | To Assess the Mean Change in Blood Pressure | Diastolic at 12 weeks | -9.40 mmHg | Standard Deviation 2.07 |
| Placebo | To Assess the Mean Change in Blood Pressure | Diastolic at 6 weeks | 4.20 mmHg | Standard Deviation 8.14 |
| Placebo | To Assess the Mean Change in Blood Pressure | Systolic at 2 weeks | -2.20 mmHg | Standard Deviation 11.5 |
| Placebo | To Assess the Mean Change in Blood Pressure | Diastolic at 2 weeks | -2.20 mmHg | Standard Deviation 8.87 |
| Placebo | To Assess the Mean Change in Blood Pressure | Systolic at 6 weeks | 2.20 mmHg | Standard Deviation 23.2 |
| Placebo | To Assess the Mean Change in Blood Pressure | Diastolic at 12 weeks | -2.00 mmHg | Standard Deviation 11.3 |
| Placebo | To Assess the Mean Change in Blood Pressure | Systolic at 12 weeks | -3.20 mmHg | Standard Deviation 13.1 |