Clinical trial NCT02893553
Conditions: Spinal Cord Injury Autonomic Dysreflexia Baroreceptor Integrity Sympathetic Integrity Vagal Integrity Autonomic Integrity Hypotensive Cognitive Function Cerebral Blood Flow Blood Pressure
Sponsor: James J. Peters Veterans Affairs Medical Center
Start date: 2016-12-01; Completion date: 2021-12-01
Enrollment: 21 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Dysregulation of blood pressure (BP), secondary to decentralized autonomic nervous system (ANS) control of the cardiovascular system, often results in chronic hypotension and orthostatic hypotension (OH) in persons with spinal cord injury (SCI), particularly in those with high cord lesions (i.e., above T6). While most hypotensive individuals with chronic SCI remain asymptomatic and do not complain of symptoms associated with cerebral hypoperfusion, evidence of reduced resting cerebral blood flow (CBF) has been reported in association with low systemic BP in the SCI and non-SCI populations. Reduced CBF in hypotensive individuals may lead to cognitive dysfunction, and we reported significantly impaired memory and marginally impaired attention processing in hypotensive individuals with SCI compared to a normotensive SCI cohort. Furthermore, we found that CBF was not increased during cognitive testing in individuals with SCI, which may contribute to impaired cognitive function compared to non-SCI controls. Although asymptomatic hypotension may have an adverse impact on cognitive function and quality of quality of life (QOL) clinical management of this condition is extremely low. In fact, we reported that while nearly 40% of Veterans with SCI were hypotensive, less than 1% carried the diagnosis of hypotension or were prescribed an anti-hypotensive medication. The discrepancy between incidence and treatment of asymptomatic hypotension in the SCI population may relate to a paucity of treatment options which are supported by rigorous clinical trials documenting safe and effective use of anti-hypotensive therapy on BP, CBF and cognitive function. We hypothesize these study medications may increase systolic blood pressure to the normal range and improve cerebral blood flow velocity. Results and conclusions will not be removed from the record.

Detailed description:
Study 1: Subjects will visit the laboratory between 3 and 9 times for 4 hours to determine the BP response to each dose of the 3 study medications (midodrine, pyridostigmine, and mirabegron). Upon arrival to the laboratory subjects will be randomized to receive midodrine, pyridostigmine, or mirabegron. Subjects will remain seated in their wheelchair for the duration of testing. Instrumentation will be applied by study personnel while subject is seated quietly, this can take up to 20 minutes. Instrumentation includes placement of 3 ECG electrodes for continuous HR monitoring and finger and brachial BP cuffs. BP, BR and HR will be recorded for 5-minutes before medication administration (baseline). After baseline, a small pill will be given with a glass of water. BP, BR and HR will be monitored for 5-minutes every 30 minutes for 4 hours after drug administration.

Study 2: Twenty will visit the laboratory on 4 occasions to determine the effects of three anti-hypotensive agents, compared to placebo, on BP, CBFv, and cognitive performance on selected neuropsychological tests. Upon arrival to the laboratory for every visit subjects will be randomized to receive midodrine, pyridostigmine, mirabegron, or matching placebo. Neither the study subject nor the investigator will know which is being administered. Subjects will remain seated in their wheelchair throughout the duration of the study session and will be closely monitored by study personnel. Instrumentation will include placement of 3 ECG electrodes for continuous heart rate (HR) monitoring, finger and brachial BP cuffs, and a Doppler ultrasound probe positioned at the left MCA for continuous CBFv monitoring. Subjects will remain quietly seated in their wheelchair for 30-minutes after instrumentation for a 5-minute recording of continuous HR, BP, and CBFv (baseline). Prior to the baseline data collection period, the first battery of cognitive tests will be administered. The study medication will be administered to the subject along with a glass of water approximately 30-minutes after arrival to the laboratory. There will be a 2 hour break period until the second cognitive battery begins.

Arms: arm 1: Study 1: is a dose escalation to determine the individualized dose of each of 3 medications (midodrine, pyridostigmine, mirabegron) that increases SBP into the normal range (111-139 mmHg). The investigator will be using midodrine hydrochloride, pyridostigmine bromide and mirabegron. arm 2: Study2: is a randomized placebo-controlled double-blinded investigation to determine the effect of the normalization of SBP on cerebral blood flow, cognitive function (memory and attention processing) and quality of life. The investigator will be using midodrine hydrochloride, pyridostigmine bromide, mirabegron and placebo.
Interventions: intervention 1: Midodrine Hydrochloride intervention 2: Pyridostigmine Bromide intervention 3: Mirabegron intervention 4: Placebo
Intervention descriptions: intervention 1: study 1 will be single blind. study 2 will be blinded randomized-control trial. intervention 2: study 1 will be single blind. study 2 will be blinded randomized-control trial. intervention 3: study 1 will be single blind. study 2 will be blinded randomized-control trial. intervention 4: placebo will only be used for study arm 2, the randomized blinded phase.

Protocol documents:
Prot_SAP_ICF_000.pdf: 
Project 9:   
To Determine the Effects of Normalizing Blood Pressure on Cerebral Blood Flow in 
Hypotensive Individuals with SCI 
 
STATEMENT OF THE PROBLEM: Dysregulation of BP, secondary to decentralized ANS control of the 
cardiovascular system, often results in chronic hypotension and orthostatic hypotension (OH) in persons with 
SCI, particularly in those with high cord lesions (i.e., above T6).  While most hypotensive individuals with chronic 
SCI remain asymptomatic and do not complain of symptoms associated with cerebral hypoperfusion, evidence 
of reduced resting cerebral blood flow (CBF) has been reported in association with low systemic BP in the SCI 
(53) and non-SCI populations (54).  Reduced CBF in hypotensive individuals may lead to cognitive dysfunction, 
and we reported significantly impaired memory and marginally impaired attention processing in hypotensive 
individuals with SCI compared to a normotensive SCI cohort (55).  Furthermore, we found that CBF was not 
increased during cognitive testing in individuals with SCI, which may contribute to impaired cognitive function 
compared to non-SCI controls (56).  Although asymptomatic hypotension may have an adverse impact on 
cognitive function (54, 57) and quality of QOL clinical management of this condition is extremely low. In fact, we 
reported that while nearly 40% of Veterans with SCI were hypotensive, less than 1% carried the diagnosis of 
hypotension or were prescribed an anti-hypotensive medication (58, 59).  The discrepancy between incidence 
and treatment of asymptomatic hypotension in the SCI population may relate to a paucity of treatment options 
which are supported by rigorous clinical trials documenting the safety and efficacy of anti-hypotensive therapy 
on BP, CBF and cognitive function. 
 
SPECIFIC AIMS: 
In hypotensive individuals with SCI: 
1. Study 9.1: To determine the dose of each of 3 agents with anti-hypotensive effects [e.g., beta (3)-
adrenoceptor agonist (mirabegron), an alpha agonist (midodrine) and an anti-cholinergic 
(pyridostigmine)] that will raise systolic BP (SBP) into the normal range (110-130 mmHg). 
2. Study 9.2: To determine the effect of each agent at the specified dose (i.e., raises SBP into the 
normotensive range) on CBF and cognitive function. 
 
PROPOSED STUDY: Subjects: Twenty hypotensive individuals with SCI who are chronically injured (> 1 year) 
and in a healthy stable condition will be recruited.  A medical history will be performed prior to investigation; 
details of the inclusion and exclusion criteria are presented (Human Subjects: Project 9: Anti-HYPO).   
 
Study 9.1: Subjects will visit the laboratory between 3 and 9 times to determine the BP effects of three different 
anti-HYPO agents.  These agents will be administered open label, to determine the effective dose for normalizing 
SBP (111-130 mmHg).  Subjects will remain seated and will be administered the study medication according to 
the dose titration (Table 4). HR and BP assessments will be recorded every 30 minutes for 4 hours post-drug.   
 
Study 9.2: Methods: Subjects will visit the laboratory 3 times and the anti-HYPO agents will be administered in 
a random and blinded order at the dose determined in Study 9.1.  Subjects will remain seated and a battery of 
cognitive tests to assess memory and attention processing will be performed with simultaneous recording of HR, 
BP, BR and CBF.  Study medication will then be administered and HR, BP, and CBF assessments will be 
recorded every 30 minutes for 4 hours.  A second battery of cognitive tests will be administered 2 hours after 
study medication.   
 
DATA AND STATISTICAL ANALYSES: Repeated measures ANCOVA models will be constructed to compare 
the effect of study medication on BP and CBF; the covariates in each model will include baseline BP and CBF.  
The alpha level will be set at 0.05 and significant omnibus effects will be decomposed with pairwise comparisons 
among anti-HYPO agents using Tukey post hoc tests on the covariate adjusted BP and CBF values.  Linear 
regression models will then be constructed to compare the relationship between change in BP and change in 
CBF among the anti-HYPO agents tested.   
 
EXPECTED RESULTS AND BENEFITS: In our proposed studies, a more precise identification of the degree of 
ANS dysfunction (Project 8) and further our understanding of the relationship between systemic BP, CBF and 
cognitive function in individuals with SCI (Project 9) will be achieved.  Data generated from these investigations 
will be used to guide clinical evaluation and treatment algorithm for improving cardiovascular, cerebrovascular 
and cognitive function in the SCI population.   


 
 
Table 4.  Dosing Schedule 
Drug 1 
Visit 1 
Visit 2 
Visit 3 
Dose 
BP response (mmHg) 
Dose 
BP response 
(mmHg) 
Dose 
Mirabegron 
(beta3 agonist) 
25 
mg 
 
≤ 110* 
50 mg 
≤ 110* 
75 mg 
111-130 
n/a 
111-130 
n/a 
≥ 140 
n/a 
≥ 140 
n/a 
Drug 2 
Visit 4 
Visit 5 
Visit 6 
Dose 
BP response (mmHg) 
Dose 
BP response 
(mmHg) 
Dose 
Pyridostigmine 
(anti-
cholinergic) 
60 
mg 
 
≤ 110* 
90 mg 
≤ 110* 
120 mg 
111-130 
n/a 
111-130 
n/a 
≥ 140 
n/a 
≥ 140 
n/a 
Drug 3 
Visit 7 
Visit 8 
Visit 9 
Dose 
BP response (mmHg) 
Dose 
BP response 
(mmHg) 
Dose 
Midodrine 
(alpha agonist) 
10 
mg 
 
≤ 110* 
15 mg 
≤ 110* 
20 mg 
111-130 
n/a 
111-130 
n/a 
≥ 140 
n/a 
≥ 140 
n/a 


























VA RESEARCH CONSENT FORM
     
Version Date: February 4, 2021
Page:  1   of  12
Subject Name: 
Informed Consent Date: 
Principal Investigator:  Jill M. Wecht, EdD
VAMC:  James J Peters
Protocol #: WEC-16-015
Title of Study: The Effect of Normalizing Blood Pressure on Cerebral Blood Flow in Hypotensive 
Individuals with SCI: blinded 
1.
Purpose of study and how long it will last: 
The purpose of this study is to measure blood pressure and blood flow to the brain during cognitive 
tests  before and after the administration of  the 3 study medications, which may have increased your 
blood pressure in Study 1. The 3 medications have been approved for experimental use in this study 
by the FDA for phase 2 clinical trial. You will be asked to visit the laboratory on 4 separate days.  The 
drugs are midodrine, pyridostigmine , and mirabegron will be given to you as a pill on 3 of the study 
visits, which will be randomized and compared to placebo (no medication). Neither you nor the study 
investigators will know what the pill contains on each of the 4 study visits.  
You are being asked to participate in this research study because you are between the age of 18 and 
85, and have had SCI for over one (1) year. This study is sponsored and funded by the National Center 
for the Medical Consequences of Spinal Cord Injury (SCI). 
You will be one of about 20 subjects with SCI who will participate in this study, or one of 40 who will 
participate across the two sites, which is being conducted at the James J. Peters VA Medical Center (JJP 
VAMC) and the Kessler Institute for Rehabilitation The time allotted  for your participation in each of 
the 4 study visits will be about 4-hours, which will occur over the course of about four weeks. Prior to 
study participation you will be screened for the following: 
Inclusion Criteria:
-
Participation in Study 1a: “titration/open label” trial
-
SCI between the ages of 18 – 85 years old
o
Any level of injury 
o
non-ventilator dependent 
o
Any AIS grade of SCI 
o
SCI duration > 1 year
o
Wheelchair dependent
-
Able to provide informed consent
-
Low blood pressure
o
Males- systolic blood pressure < 110 mmHg and/or diastolic BP < 70 mmHg
o
Females- systolic blood pressure < 100 mmHg and/or diastolic BP < 70 mmHg
Exclusion Criteria: 
-
Current illness or infection
-
Individuals with frequent or severe autonomic dysreflexia
o
More than 3 symptomatic events per week
VA    Department of 
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JJPVAMC IRB
Effective Date:
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VA RESEARCH CONSENT FORM
     
Version Date: February 4, 2021
Page:  2   of  12
Subject Name: 
Informed Consent Date: 
Principal Investigator:  Jill M. Wecht, EdD
VAMC:  James J Peters
Protocol #: WEC-16-015
Title of Study: The Effect of Normalizing Blood Pressure on Cerebral Blood Flow in Hypotensive 
Individuals with SCI: blinded 
o
BP ≥140/90 mmHg
o
Significant adverse subjective symptoms reporting
-
Hypertension 
-
Any neurological condition other than SCI (Alzheimer’s disease, dementia, stroke, 
multiple sclerosis, Parkinson’s disease, etc.)
-
History of epilepsy or other seizure disorder
-
History of traumatic brain injury (TBI) 
-
Liver or kidney disease.
-
Bladder issuing including blockage of the urine and/or weak urine stream. 
-
Diagnosis of a psychiatric disorder such as schizophrenia or bipolar disorder
-
Known artery disease, heart failure, AV block, and irregular heartbeat. 
-
Any allergies to aspirin, mirabegron, pyridostigmine bromide, midodrine 
hydrochloride, polyethylene oxide, polyethylene glycol, hydroxypropyl cellulose, 
butylated hydroxytoluene, magnesium stearate, hypromellose, yellow ferric oxide, and 
red ferric oxide.
-
Mini mental status exam score of less than 24
-
Vision impaired- more than 20/60 in worst eye (with prescription eyewear)
-
Major surgery in the last 30 days
-
Your prescription medications will be reviewed by the study investigators and research staff. 
If you are currently taking medications to treat any of the following please make the 
investigators aware:
o
Depression, Schizophrenia, ADHA
o
Pain (opioids)
o
Infection or illness (antibiotics)
o
Erectile dysfunction (Viagra, Cialis, etc.)
o
Overactive bladder 
o
High or low blood pressure 
o
Migraine headaches
o
Malaria
o
Asthma 
-
Please talk to the research staff if you have any questions about your medicaitons; we 
may contact your doctor to discuss.
-
Pregnant*
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Effective Date:
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VA RESEARCH CONSENT FORM
     
Version Date: February 4, 2021
Page:  3   of  12
Subject Name: 
Informed Consent Date: 
Principal Investigator:  Jill M. Wecht, EdD
VAMC:  James J Peters
Protocol #: WEC-16-015
Title of Study: The Effect of Normalizing Blood Pressure on Cerebral Blood Flow in Hypotensive 
Individuals with SCI: blinded 
2.
Description of the Study Including Procedures to be Used:
If you consent to participate in this research study, you will visit the laboratory at the JJPVAMC (7A-
13S) 4 times for about 4 hours each visit. You will refrain from caffeine, alcohol, heavy exercise, and 
smoking for 12 hours prior to arrival and you will refrain from taking sildenafil (Viagra), tadalafil 
(Cialis), or other similar medications, for 2-days prior to each of your study visits. Prior to data 
collection a baseline blood draw will be collected. You will remain  seated in your wheelchair for a 
minimum of 20 minutes while the research team applies instrumentation. Three sticky electrodes will 
be placed on your chest and abdomen area to monitor your heart rate and respiratory (breathing) 
rate.  A blood pressure cuff will be placed around your upper right arm and a small blood pressure 
cuff will be placed on your left middle or ring finger. We will place a plastic harness on your head, 
apply gel to your forehead and place an ultrasound probe against your head. We will monitor your 
blood pressure, respiration rate, heart rate and blood flow to your brain (CBF) for 5 minutes while 
you rest quietly (baseline) prior to administration of the study medication.  Following the baseline 
data  collection  a  series  of  cognitive  tests  focused  on  assessing  memory  and  attention  will  be 
administered. You will then be given  pills with a glass of water. The pills will contain either placebo, 
pyridostigmine, mirabegron, or midodrine. During each of the four visits, you will take only 1 type of 
medication or placebo. If you complete all 4 visits, you will have taken one of each medication 
including placebo.   You will not know which of the study medications or placebo you will be taking at 
any given visit.  The effective dosage for each medication was determined from your participation in 
the previous “titration” trial. After taking the study medication, heart rate, respiratory rate, blood 
pressure and blood flow to the brain will be monitored for 4-hours and a second battery of cognitive 
tests, similar to the first battery, will be administered 2 hours after taking the medication. After you 
finish the second cognitive tests a final blood draw will be performed. Each of the medications we 
have chosen have short duration of action so any bad reaction should last for a short period of time. 
But if at any time you feel uncomfortable, we will immediately stop the study medication and all 
testing and will monitor your heart rate, breathing rate, and blood pressure very closely until you 
recover.
VA    Department of 
Veterans Affairs
 
JJPVAMC IRB
Effective Date:
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VA RESEARCH CONSENT FORM
     
Version Date: February 4, 2021
Page:  4   of  12
Subject Name: 
Informed Consent Date: 
Principal Investigator:  Jill M. Wecht, EdD
VAMC:  James J Peters
Protocol #: WEC-16-015
Title of Study: The Effect of Normalizing Blood Pressure on Cerebral Blood Flow in Hypotensive 
Individuals with SCI: blinded 
Table 1: Protocol Timeline
Time Point
Pre-1
Pre-2
Pre-3
Drug
Post-1
Post-2
Post-3
Post-4
Time (min)
0-10
10-25
25-30
30
60-120
120-180
180-
240
240-
300
Heart Rate
instrumentation
1x
1x
 
2x
2x
2x
2x
Breathing Rate
1x
1x
2x
2x
2x
2x
Drug 
administration
x
 
Beat-to-beat BP
1x
1x
2x
2x
2x
2x
Manual BP
5x
5x
4x
4x
4x
4x
CBFv
1x
1x
1x
1x
1x
1x
AD Survey
1x
1x
1x
1x
1x
1x
Blood Draws
1x (3.6) 
teaspoons 
or 18mL
1x (3.6) 
teaspoons 
or 18mL
Cognitive Tests
1x
 
 
 
1x
 
 
Heart Rate & Respiration Rate : Three electrodes (small sticky pads) will be placed on your chest 
and abdomen to continuously monitor your heart rate and respiratory rate during each study visit. 
Heart rate will be monitored and recorded for 5-minutes during the baseline period and at 30-minute 
intervals after administration of the study medications and during the cognitive test. 
Blood Pressure: Blood pressure will be monitored and recorded from your right upper arm using 
standard  procedures  at  1-minute  intervals  during  baseline  and  at  30-minute  intervals  after 
administration of the study medications.  Finger blood pressure will be monitored continuously from 
your left middle or ring finger on a beat-to-beat basis during the baseline period.  Beat-to-beat blood 
pressure will be recorded throughout the cognitive tests and at 30-minute intervals throughout the 4-
hour period following administration of the study medications.   
Cerebral Blood Flow: CBF will be monitored and recorded using a small Doppler ultrasound probe (a 
noninvasive test that measures brain blood flow) with ultrasound gel that will be placed over your left 
temple to measure blood flow velocity through your middle cerebral artery. The Doppler probe will 
VA    Department of 
Veterans Affairs
 
JJPVAMC IRB
Effective Date:
March 2, 2021


VA RESEARCH CONSENT FORM
     
Version Date: February 4, 2021
Page:  5   of  12
Subject Name: 
Informed Consent Date: 
Principal Investigator:  Jill M. Wecht, EdD
VAMC:  James J Peters
Protocol #: WEC-16-015
Title of Study: The Effect of Normalizing Blood Pressure on Cerebral Blood Flow in Hypotensive 
Individuals with SCI: blinded 
be held in place with a head harness which will be tightened so that the probe doesn’t move around 
during testing.
Cognitive Tests: These tests evaluate different types of cognitive function such as your short-term, 
and long-term memory, attention processing speed, and executive function. During this time we will 
continuously monitor and record your heart rate, breathing rate, blood pressure and blood flow to 
your brain using the equipment attached to you. 
Autonomic Dysreflexia (AD) Symptoms Survey: Autonomic dysreflexia is a condition where blood 
pressure increases higher than normal, usually because of a painful or non-painful stimulus below the 
level of your spinal cord injury. Some of the most common causes of AD relate to bowel or bladder 
fullness, tight clothing, or pressure from being in a position for too long, but there may be other 
causes that we are not aware of.  You will be asked to complete an AD symptoms survey during each 
study visit, which will be used to determine your experience with AD over the 7-days prior to the 
study  visit.   This  survey  contains  questions  related  to  symptoms  you  may  have  experienced, 
information about your blood pressure at that time, and possible causes of the AD.
Blood Draws: Blood will be drawn from a vein in your arm or hand twice over the course of each 
study visit. Each blood collection tube will contain about 1.2 teaspoon (6mL) of your blood. Three 
blood samples will be taken before baseline data collection in the seated position. Three more 
samples will be taken after the second cognitive test while you are seated. A certified and trained 
researcher will gently insert a very small needle into the vein in your arm to collect the blood. Once 
the blood has been collected, the needle will be removed and the puncture site will be cleaned and 
covered. At each study visit, six tubes of 6mL of blood will be collected. A total amount of 144mL of 
blood will be collected at the end of the four study visits.
All specimens obtained during this study will be stored in the Basic Science Laboratory at The Center 
of Excellence on the Medical Consequences of Spinal Cord Injury located at the James J. Peters 
Veterans Affairs Medical Center, Bronx, NY. All samples will be labeled with a number randomly 
assigned to you, along with the date and information regarding the study. Samples will be stored for 
future analysis specifically related to this study. Samples will be stored until all data related to this 
study has been analyzed and at the end of this period specimens will be destroyed.
3.
Description of any Procedures that may Result in Discomfort or Inconvenience:
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JJPVAMC IRB
Effective Date:
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VA RESEARCH CONSENT FORM
     
Version Date: February 4, 2021
Page:  6   of  12
Subject Name: 
Informed Consent Date: 
Principal Investigator:  Jill M. Wecht, EdD
VAMC:  James J Peters
Protocol #: WEC-16-015
Title of Study: The Effect of Normalizing Blood Pressure on Cerebral Blood Flow in Hypotensive 
Individuals with SCI: blinded 
You have been told that the study described above may involve the following discomforts: 

You may experience some discomfort when electrodes are removed from skin and some skin 
irritation at the site of electrode placement.

You may experience some discomfort when the blood pressure cuffs around your upper arm 
and your finger is inflated. 

You may feel discomfort with the harness around your head that is used to secure the 
ultrasound probe to your head for assessment of brain blood flow.

Possibly frustration may occur during the thinking tests. You will be encouraged to take 
breaks as needed and you may stop a test at any time and for any reason. 

Since this research may have unknown effects on an unborn child and should not be done 
during pregnancy, it is necessary for a pregnancy test to be done first.  To your knowledge 
you are not pregnant at the present time. You also agree to avoid becoming pregnant (use 
contraceptives, take precautions against becoming pregnant, etc.) during this study.

You may experience some discomfort when the needle is being placed in your arm vein 
during the blood draws. 
4.
Expected Risks of Study:

Heart rate, breathing rate, and blood pressure: are all non-invasive measurements and are 
not associated with any known risks. 

You may experience  pain, bruising, and rarely fainting or infection from the blood draws. 

Your blood pressure may be elevated above what is considered to be the normal range 
(>140/90 mm Hg) following midodrine, pyridostigmine, and mirabegron administration. If 
this happens, we will take action to help reduce higher pressure; we will loosen any tight 
clothing or braces that you may be wearing; and we will help you check and empty your 
bladder or bowel. If your blood pressure remains high for more than 30 minutes after we 
take these measures, then we may  provide medication to lower your pressure back to 
normal. The medication of choice will be sub-lingual (under the tongue) nitroglycerin. 

If after 4-hours of testing your BP remains above your baseline but is not in the hypertensive 
range  (>139/89  mmHg),  you  will  be  sent  home  with  a  24-hour  BP  Holter  monitor 
(Vasomedical-BIOXTM 2301 Wuxi, Jiangsu, China). The monitor will be programmed to obtain 
BP readings every 20 minutes during the daytime and at 30-minute intervals during the 
nighttime. A study coordinator or the PI will follow-up with phone calls to you while you are 
at home to assess any side effects and document BP changes. 

You will be asked to immediately report any significant AE you may feel after leaving the 
laboratory.   Symptoms  which  you  should  be  particularly  aware  of  include:  headache, 
VA    Department of 
Veterans Affairs
 
JJPVAMC IRB
Effective Date:
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VA RESEARCH CONSENT FORM
     
Version Date: February 4, 2021
Page:  7   of  12
Subject Name: 
Informed Consent Date: 
Principal Investigator:  Jill M. Wecht, EdD
VAMC:  James J Peters
Protocol #: WEC-16-015
Title of Study: The Effect of Normalizing Blood Pressure on Cerebral Blood Flow in Hypotensive 
Individuals with SCI: blinded 
pounding in the ears, blurry vision, nausea, goosebumps, chills and spasms; please alert the 
research staff if you experience any of these symptoms in greater frequency or severity 
during the experiment or after you leave the laboratory.

In order to diminish the possible risks of interaction between the study medications and 
other  medications  you may be taking, you may be  asked  to avoid  taking prescription 
medications on the day of the study,  which should be approved by your primary physician. 

There may be interactions between the study medication and prescription medications you 
may be taking.  In order to lower the risk to you the research staff will monitor your 
medications and may contact your doctor if needed. Medications prescribed for conditions 
not mentioned in the exclusion criteria, may have minor or moderate risks, (meaning the 
effects are considered tolerable and in most cases there is no need for medical intervention), 
and may be permitted, but decisions about your study participation should be made by study 
personnel in conjunction with you and your doctor.   

Symptoms of autonomic dysreflexia (AD) may become more frequent or worse while taking 
midodrine, mirabegron and pyridostigmine.

Common side effects of all three medications are dizziness, nausea, blurred vision , headache, 
bladder pain, difficulty, painful, and/or burning urination. Also, an urge to urinate or urine 
retention. 

Midodrine risks (≤8% likely) include: cardiac awareness (irregular heartbeat or shortness 
of breath), pounding in the ears, increased dizziness, slow pulse, fainting, tingling and itching 
of the scalp, goosebumps, chills, constipation, superficial venous thrombosis (a blood clot in a 
vein), vascular ischemia (blockage of blood supply in an artery), and temporary muscle 
spasms.

Pyridostigmine  risks: (≤2% likely) include; upset stomach, abdominal cramps, increased 
saliva/mucus, urinary frequency and/or urgency, nausea, increased flatulence, wheezing, 
decreased pupil size, increased sweating or cold sweat, pale skin, watery eyes, warmth or 
tingly feeling, and rash or itching.

Mirabegron risks (0.2% likely) include: abdominal or stomach pain, dry mouth, difficultly 
with breathing, muscle aches, diarrhea, constipation , bloating, sinus pain, and sore throat. 

Since this research may have unknown effects on an unborn child and should not be done 
during pregnancy, it is necessary for a pregnancy test to be done first.  To your knowledge 
you are not pregnant at the present time. You also agree to avoid becoming pregnant (use 
contraceptives, take precautions against becoming pregnant, etc.) during this study.

As with any research, there may be unforeseen risks and discomforts.  A medical doctor 
associated with the study will be available to treat any medical emergency that may develop.
VA    Department of 
Veterans Affairs
 
JJPVAMC IRB
Effective Date:
March 2, 2021


VA RESEARCH CONSENT FORM
     
Version Date: February 4, 2021
Page:  8   of  12
Subject Name: 
Informed Consent Date: 
Principal Investigator:  Jill M. Wecht, EdD
VAMC:  James J Peters
Protocol #: WEC-16-015
Title of Study: The Effect of Normalizing Blood Pressure on Cerebral Blood Flow in Hypotensive 
Individuals with SCI: blinded 
5.
Expected Benefits of the Study:
There may be no direct benefit to you from this study, but information learned may help others.
6.
Other Treatments Available:
Participation in the  study is voluntary and  you understand that the  only alternative  is to  not 
participate. 
7.
Use of Research Results:
We will let you and your physician know of any significant new findings made during this study which 
may affect your willingness to participate. All research material generated from the study will remain 
in the possession of Dr. Wecht and her study team. De-identified electronic data will be stored on 
secured VA networks, behind VA firewalls, in access-restricted folders. Coded physical data will be 
stored at the JJP VAMC in locked file cabinets behind locked doors. Access to the research materials 
generated from the study will be restricted to Dr. Wecht’s research team. Your medical records will be 
maintained according to this medical center’s requirements and all electronic and hard copy Research 
Records  will  be  retained  according  to  National  Archives  and  Records  Administration,  Records 
Schedule Number RCS-10-1.
□__________ By checking this box and initialing, you agree to be contacted by the Principal Investigator 
or her investigative team at a future date for additional studies being conducted in the National 
Center for the Medical Consequences of SCI. 
If results of this study are reported in medical journals or at meetings, you will not be identified by 
name,  by  recognizable  photograph,  or  by  any  other  means  without  your  specific  consent.  No 
information by which you can be identified will be released or published unless required by law. In 
order to comply with federal regulations, research records identifying you may be reviewed by the 
following: Authorized representatives of the Bronx VAMC (e.g. Institutional Review Board, Research 
Compliance Officer) and VA, including the Office of Research Oversight (ORO), Federal Agencies such 
as the Government Accounting Office (GAO), VA Office of Inspector General (OIG), Food and Drug 
Administration (FDA), and the Office for Human Research Protections (OHRP).
Because this research involves articles regulated by the FDA, the FDA may choose to inspect and copy 
medical or research records that identify individual research subjects”. If this study was initiated on 
VA    Department of 
Veterans Affairs
 
JJPVAMC IRB
Effective Date:
March 2, 2021


VA RESEARCH CONSENT FORM
     
Version Date: February 4, 2021
Page:  9   of  12
Subject Name: 
Informed Consent Date: 
Principal Investigator:  Jill M. Wecht, EdD
VAMC:  James J Peters
Protocol #: WEC-16-015
Title of Study: The Effect of Normalizing Blood Pressure on Cerebral Blood Flow in Hypotensive 
Individuals with SCI: blinded 
or  after  March  7,  2012,  a  description  of  this  clinical  trial  will  be  available  on 
http://www.ClinicalTrials.gov, as required by U.S. Law.  This web site will not include a summary of 
the results.  You can search this web site at any time.
8.
Special Circumstances:
If you are a patient, a copy of this consent form will be placed in your medical record.
9.
Compensation and/or Treatment in the Event of Injury:
The VA must provide necessary medical treatment to a research subject injured by participation in a 
research project approved by a VA R&D Committee and conducted under the supervision of one or 
more  VA  employees.  Further  information  about  compensation  and  medical  treatment  may  be 
obtained from the medical administration service at this VA medical center. A veteran-participant 
does not have to pay for care received as a participant in a research project, except in accordance with 
federal law that certain veterans have to pay co-payments for medical care and services provided by 
the VA.
10.
Voluntary Participation:
You are not required to take part in this study; your participation is entirely voluntary. You can refuse 
to participate in this study or withdraw your participation in this study after you consent without 
penalty or loss of VA or other benefits to which you are entitled. During the course of the study, you 
will be told about any new findings within the investigation or about information reported in the 
literature or reported verbally to the investigators that might affect your willingness to remain in the 
study. A signed copy of this consent form will be given to you.
11.
Termination of Participation:
You can refuse to participate now or you can withdraw from the study at any time after giving your 
consent. This will not interfere with your regular medical treatment, if you are a patient. The 
investigator also has the right to withdraw you from the study at any time for reasons including, but 
not limited to, medical concerns (your health and safety are in jeopardy with continued participation 
in the study), non-compliance (you miss several scheduled appointments without notification) and 
protocol deviations (exclusion/inclusion criteria change and you are no longer eligible to participate).
12.
Costs and Reimbursements:
As a veteran or non-veteran, you will not be charged for any treatments or procedures that are part of 
this study. For veterans who are required to pay co-payments for medical care and services provided 
VA    Department of 
Veterans Affairs
 
JJPVAMC IRB
Effective Date:
March 2, 2021


VA RESEARCH CONSENT FORM
     
Version Date: February 4, 2021
Page:  10   of  12
Subject Name: 
Informed Consent Date: 
Principal Investigator:  Jill M. Wecht, EdD
VAMC:  James J Peters
Protocol #: WEC-16-015
Title of Study: The Effect of Normalizing Blood Pressure on Cerebral Blood Flow in Hypotensive 
Individuals with SCI: blinded 
by VA, these co-payments will continue to apply for medical care and services provided by VA that are 
not part of this study.  Reimbursement typically takes 6-8 weeks to arrive by Electronic Transfer Fund 
(EFT)  and  12-14  weeks  to  arrive  by  check.  You  understand  that  if  you  choose  to  receive 
reimbursement through EFT, you will be required to provide the research staff information that 
includes; name of your bank, routing number and account number. 
You have been told that you will receive up to $300 for participation in this research study according 
to the following schedule:
o
Visit 1 - $75.00
o
Visit 2 - $75.00
o
Visit 3-$75.00
o
Visit 4- $75.00
You understand that payment will be processed after each study visit based on the above schedule, 
and that you will be paid for each study visit you attend and complete. You understand that if you 
cannot complete all study visits you will be paid for the testing sessions that you complete. 
13.
Contact Person(s):
If you have any questions, at any time, about this research, or want to discuss any possible study-
related injuries, please call telephone number 718-584-9000, ext. 3122 for Dr. Wecht. In addition 
after-hours you can contact Dr. Wecht at (201) 390-0487 or the medical doctor affiliated with this 
study:  Dr. William Bauman at (914) 329-4772. 
I understand that should I wish to discuss my participation in this study with any other doctor or 
layperson, I can contact Mary Sano, Ph.D. ACOS/R&D Program by requesting an appointment at (718) 
741-4228 hospital extension 4228, first floor in the research building, room 1F-01 If I have questions, 
concerns and/or complaints or to offer input. 
RESEARCH SUBJECTS' RIGHTS: 
You have read or have had read to you all of the above.  Dr. Jill M. Wecht, EdD or her delegate has 
explained the study to you and answered all of my questions. You have been told of the risks or 
VA    Department of 
Veterans Affairs
 
JJPVAMC IRB
Effective Date:
March 2, 2021


VA RESEARCH CONSENT FORM
     
Version Date: February 4, 2021
Page:  11   of  12
Subject Name: 
Informed Consent Date: 
Principal Investigator:  Jill M. Wecht, EdD
VAMC:  James J Peters
Protocol #: WEC-16-015
Title of Study: The Effect of Normalizing Blood Pressure on Cerebral Blood Flow in Hypotensive 
Individuals with SCI: blinded 
discomforts and possible benefits of the study. You have been informed of other choices of treatment 
available to me.  
I understand that I do not have to take part in this study, and my refusal to participate will 
involve no penalty or loss of rights to which I am entitled. I may withdraw from this study at 
any time without penalty or loss of VA or other benefits to which I am entitled.   
The results of this study may be published, but my records will not be revealed unless required by 
law. This study has been explained to me. I have had a chance to ask questions. I voluntarily consent 
to participate in this study.  I will receive a signed copy of this consent form.
Subject Signature
Date
Time
Person Obtaining Informed Consent 
(Print Name) 
(Investigator or Delegate as indicated on 
Assurance Page)
Signature of Person 
Obtaining Informed 
Consent
Date
VERBAL CONSENT IF THE PARTICIPANT LACKS UPPER LIMB FUNCTIONS TO 
COMFORTABLY WRITE
________________________________ is unable to sign the consent form due to impaired arm 
function. I certify that I have carefully explained the purpose and nature of this research to him/her 
VA    Department of 
Veterans Affairs
 
JJPVAMC IRB
Effective Date:
March 2, 2021


VA RESEARCH CONSENT FORM
     
Version Date: February 4, 2021
Page:  12   of  12
Subject Name: 
Informed Consent Date: 
Principal Investigator:  Jill M. Wecht, EdD
VAMC:  James J Peters
Protocol #: WEC-16-015
Title of Study: The Effect of Normalizing Blood Pressure on Cerebral Blood Flow in Hypotensive 
Individuals with SCI: blinded 
in appropriate language and he/she has had an opportunity to discuss it with me in detail. I have 
answered all of his/her questions and he/she has consented to participate in this research. I, therefore, 
am signing the consent form to document that he/she has given his/her consent to participate in this 
research study.
Person Obtaining Consent:                                                    
Name: ________________________________
Signature: ______________________________
Date: ________________________
Witness Name: __________________________
Signature: ______________________________
Date: ______________________
VA    Department of 
Veterans Affairs
 
JJPVAMC IRB
Effective Date:
March 2, 2021