Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT05998629 |
| Other study ID # |
7772 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
July 1, 2024 |
| Est. completion date |
December 1, 2025 |
Study information
| Verified date |
January 2024 |
| Source |
Milton S. Hershey Medical Center |
| Contact |
Robert Vender |
| Phone |
17175316525 |
| Email |
rvender[@]pennstatehealth.psu.edu |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Cystic fibrosis (CF) is a multisystem autosomal recessive inherited disease affecting
approximately 75,000 individuals in USA. The sweat chloride (Cl) test remains the gold
standard for diagnosis of CF but still has a number of limitations. The objectives of this
study are: 1)To evaluate a skin-interfaced colorimetric bifluidic sweat device with two
synchronous channels as a potential low-cost but potentially accurate test to diagnoses
cystic fibrosis (CF) and 2) To evaluate measurements of sweat chloride (Cl) using this same
system in comparison to the standard clinical laboratory procedures routinely performed in
the Clinical Laboratory at Penn State Health Milton S. Hershey Medical Center (PSH-HMC),
Hershey, PA for assessment of the diagnosis of CF. This is a single institution study
performed solely at PSH-HMC. Study participants will include 1) adults 18 years of age or
older capable of providing signed and dated informed consent, 2) subjects with an established
known diagnosis of cystic fibrosis (CF) or healthy volunteers, and 3) able to understand and
speak English language. Exclusion criteria include: 1) any medical condition or disorder
known to potentially interfere with accurate measurements of sweat chloride and 2) inability
to understand and speak the English language. Cystic Fibrosis (CF) subjects will be
identified from the population of eligible patients receiving medical care at Penn State
Health- Milton S. Hershey Medical Center (PSH-HMC). Healthy donor volunteers will be
recruited from various members of the PSH-HMC CF clinical care team, members of the Division
of Allergy, Pulmonary and Critical Care (both faculty and trainees) at PSH-HMC, and
PSU-University Park research team. The total projected number of combined enrolled subjects
is 30. This is a single day single time study that will require approximately 60 minutes of
subject participation. Potential risks include a) side effects from pilocarpine iontophoresis
sweat test collection (pain, skin discomfort, blisters, rarely burns and b) loss of
confidentiality. There will be no cost to subjects for study participation. There will be no
reimbursement financially for study participation. There is no benefit to subjects for study
participation. There is the potential benefit to medical science via identification of
improved method to accurately measure sweat chloride for diagnosis of CF.
Description:
Background: Cystic fibrosis (CF) is a multisystem autosomal recessive inherited disease
affecting approximately 75,000 individuals in USA. The sweat chloride (Cl) test remains the
gold standard for diagnosis of CF but still has a number of limitations including 1) common
inability to recover enough sweat volume for test accuracy, termed "quantity not sufficient"
limitation, 2) difficulty of performing in young children and infants, 3) absence of point of
care (POC) simplicity and need to schedule prolonged (> 1 hour) appointment with high
resource and personnel utilization, and 4) still a range of values without one specific
diagnostic cut-off measurement thus creating sweat Cl classifications of negative (normal),
indeterminant, and positive (diagnostic). Multiple publications already exist validating the
use of POC skin-interfaced micro fluidic colorimetric systems in attempts to overcome these
limitations of the still standard of care macroduct sweat collection and analysis system. The
current proposed investigational diagnostic (not therapeutic) device introduces a
skin-interfaced colorimetric bifluidic sweat collection and analyses device with two
synchronous channels to quantify sweat rate and biomarkers (for this study Cl) in real-time,
even during uncertain sweat conditions and activities. This proposed bifluidic system could
provide accurate analysis of biomarkers (including Cl) based upon instantaneous sweat rate.
For consistent of data accrual and analyses in this proposed study, for both methods of sweat
collection pilocarpine iontophoresis will be the method of sweat stimulation. This
skin-interfaced colorimetric bifluidic sweat device with two synchronous channels device is a
closed system design to reduce evaporation and resists contamination from the external
environment. This low-cost yet highly accurate device provides opportunities for clinical
sweat analysis and disease screening in remote and low-resource settings which is currently
non-existent with standard clinical measurements of sweat Cl. In addition, this device can be
easily adapted for other biomarkers, when corresponding colorimetric reagents are exploited.
Inclusion Criteria: 1) Adults 18 years of age or older capable of providing signed and dated
informed consent, 2) Subjects with an established know diagnosis of cystic fibrosis (CF) or
healthy volunteers, 3) Competent to understand written and spoken English language.
Exclusion Criteria: Participants receiving medications or with known disorders that can cause
errors in sweat test analysis. Common causes of potential error inducing factors in sweat
test determination include Lithium therapy, mineralocorticoid hormone therapy, adrenal
insufficiency, glycogen storage diseases, hypothyroidism, hypoparathyroidism, nephrogenic
diabetes insipidus, G6PD deficiency, ectodermal dysplasia, or any skin or soft tissue
disorders that could affect obtaining the necessary volume and quality of sweat.
Non-English-speaking subjects will be excluded.
Study Design: This is a single institution study to be performed entirely at the Penn State
Health Milton S. Hershey Medical Center (PSH-HMC), Hershey, PA. This is only a single day,
single time study, i.e. VISIT 1 and DAY 1 ONLY. The study involves minimal risk. There is no
anticipated benefit to subjects for study participation. Total subject participation time
will be approximately 60 minutes, after which subjects' participation will end. The total
combined estimated enrollment for both health volunteer subjects and CF subjects will be 30.
Two sweat chloride samples and measurements as per study procedures will be obtained
simultaneously from both arms using pilocarpine iontophoresis.
Study Procedures: 1) PSH-HMC Clinical Laboratory Department of Pathology SOP dated
14-Nov-2022 "Macroduct Sweat Collection" will be complied for attainment of the sample for
which sweat chloride will be measured at PSH-HMC. The site for this procedure is Suite 520 at
the University Physicians Center, Hershey, PA. After completion of pilocarpine iontophoresis
and following collection of sweat specimens inside the macroduct tubing, the sweat will then
be eluted and analyzed separately. PSH-HMC sample chloride biochemical analyses: a) add
reached 12 μL as indicated in the microfluidic device. The measured color change distance
will be used to determine the chloride concentration according to the linear relationship.2N
nitric acid and s-Diphenylcarbazone, b) rinse with 0.005N mercuric nitrate and titrate to
very light purple color and record volume of mercuric nitrate, c) prepare control standards,
d) calculate the chloride result using the EXCEL calculation template.
2) PSU-UP sample chloride biochemical analyses: The real-time quantification of sweat rate
and chloride will also be pursued with a skin-interfaced colorimetric microfluidic sweat
device developed at Penn State University- University Park, PA (PSU-UP). In brief, the skin
of the human subjects will first be washed with soap and water and dried with disposable
paper. The device will be attached to the skin near pilocarpine iontophoresis. The experiment
will end after the collected sweat.
Risks: 1) The attainment of the sweat chloride sample for analyses involves only minimal
risk. Obtaining a sweat chloride sample entails approximately 45-60 minutes for volume
collections plus as per the standard process of pilocarpine iontophoresis (which is the
chemical and electrical process used to stimulate the production of sufficient volumes of
sweat) for approximately 5-10 minutes. CF patients may have had this sweat chloride test
performed at an early age as part of their diagnostic evaluation for CF. During this time
period of collection a electrical charge will be delivered via a battery device to the two
electrodes attached to the skin of both forearms which may cause discomfort such as numbness,
tingling, pins and needles sensation or actual pain, and is expected to resolve with
termination of tests without any expectation of long term sequelae or injury. If such
discomfort becomes excessive or intolerant as per study participant, the process will be
terminated. When the pilocarpine iontophoresis procedure is completed the skin under the gel
pads usually looks red and puffy. Occasionally small whitish blisters can appear. Both
conditions fade quickly and usually disappear without two hours. Very rarely small burns or
blisters can occur. This happens in less than 1 in 50,000 patients. Two samples will be
obtained from separate arms simultaneously at a single timepoint. 2) The recovery of any
private health related information always creates the potential of risk of disclosing this
information beyond the intent of this research study. In accordance with PSH-HMC and Federal
guidelines and policies , all precautions will be taken to avoid this risk including the
"coding" of personal identifiable information and protected health information (including
name, medical record number [if available], age, date of birth, gender, race, medications)
and the security of any information linking this code to personal health and personal
identifiable information being secured in a locked office of Dr. Vender in Biomedical
Research Building (C5860F).
