Postural Tachycardia SyndromeNCT03218761
POTS NET mRNA Functional Correlation With NET Activity
An observational study of Postural Tachycardia Syndrome, run by Vanderbilt University Medical Center at 1 site in United States.
Trial summary
DNA Acetylation can be responsible for significant down-regulation of transcription of the Norepinephrine Transporter (NET). NET is an important clearance transporter that removes norepinephrine (NE) from sympathetic neuronal synapses. Read more about this study
- Who is it for?
- Ages 13 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Postural Tachycardia Syndrome
- What is being tested?
- NET mRNA level, Plasma catechols and Urine Catechols
- How many people
- 200 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Jul 2017to 31 Dec 2029
- How long will I take part?
- 2 Days
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 to 80 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Patients with POTS and Subjects without POTS who are not on drugs that inhibit the norepinephrine transporter and are willing to give their informed consent (or assent and parental consent) to participate in the project.
Who may be able to join
- • Postural Tachycardia Syndrome
- Previously diagnosed with POTS
- Control Subjects
- Not diagnosed with POTS
- Age between 13-80 years
- Male and female subjects are eligible.
- Able and willing to provide informed consent (if ≥18 years) or assent with parental consent (if age 13-17 years)
Who cannot join
- • Inability to give, or withdrawal of, informed consent
- Use of serotonin-norepinephrine reuptake inhibitors (SNRI) or NET inhibitors within 1 month
- o These drugs pharmacologically block NET activity
- Use of Tricyclic antidepressants within 1 week
- o Many tricyclic antidepressants pharmacologically block NET activity
- Other factors which in the investigator's opinion would prevent the subject from completing the protocol.
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
Official title: Validation of Norepinephrine Transporter (NET) mRNA as a Measure of Functional NET Expression in Postural Tachycardia Syndrome (POTS)
DNA Acetylation can be responsible for significant down-regulation of transcription of the Norepinephrine Transporter (NET). NET is an important clearance transporter that removes norepinephrine (NE) from sympathetic neuronal synapses. Very low levels of NET can "cause" Postural Tachycardia Syndrome (POTS) or make these patients more susceptible to certain medications. Quantified NET messenger RNA (mRNA) levels from a peripheral blood sample may be able to assess NET availability, which is simpler than older methods. This has not been validated against NET function. In this protocol, the investigators seek to assess whether these NET mRNA levels correlate with NET function. The investigators will assess the DHPG (NET dependent NE metabolite):NE ratio in POTS patients and control subjects from both plasma and urine samples.
Read the detailed description
Work from The Baker Institute in Melbourne, Australia has shown that there can be significant epigenetic modification of the Norepinephrine Transporter (NET). DNA Acetylation can be responsible for significant down-regulation of transcription. NET is an important clearance transporter that removes norepinephrine (NE) from sympathetic neuronal synapses.Very low levels of NET can produce a hyperadrenergic phenotype and can "cause" Postural Tachycardia Syndrome (POTS). The Baker Institute researchers have started using quantified NET mRNA levels from a peripheral blood sample to assess NET availability. This is a huge advance due to its simplicity, in contrast to a prior method which involved a vein biopsy to look at the level of protein expression.
In this protocol, the investigators seek to assess whether these NET messenger RNA (mRNA) levels correlate with NET function. When NET transports NE back into presynaptic neurons, a high percentage gets converted to a metabolite (DHPG) and then released into the blood stream. Therefore, the ratio of DHPG:NE ratio is decreased with reduced NET activity. The investigators will assess this DHPG:NE ratio in POTS patients and control subjects from both plasma and urine samples.
- Conditions
- Postural Tachycardia Syndrome
- Being tested
- NET mRNA level, Plasma catechols, Urine Catechols
- Keywords
- norepinephrine, norepinephrine transporter
- Medical subject headings
- Postural Orthostatic Tachycardia Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NET mRNA levelDiagnostic test
quantification of mRNA to the Norepinephrine Transporter (NET)
Plasma catecholsDiagnostic test
plasma for assay of norepinephrine (NE), DHPG (intraneuronal metabolite of NE), and other catechols
Urine CatecholsDiagnostic test
urine for assay of norepinephrine (NE), DHPG (intraneuronal metabolite of NE), and other catechols
| Study group | Role | What they receive |
|---|---|---|
| POTS Patients | Patients who self-identify as having Postural Tachycardia Syndrome.
They will have assessment of NET mRNA levels, supine plasma catechols, standing plasma catechols, and urine catechols. Receives: Diagnostic Test: NET mRNA level; Diagnostic Test: Plasma catechols; Diagnostic Test: Urine Catechols | |
| Control Subjects | Subjects who do not have Postural Tachycardia Syndrome.
They will have assessment of NET mRNA levels, supine plasma catechols, standing plasma catechols, and urine catechols. Receives: Diagnostic Test: NET mRNA level; Diagnostic Test: Plasma catechols; Diagnostic Test: Urine Catechols |
What is being measured
The primary outcome is the main question the study is designed to answer.
Supine Plasma DHPG:NE correlation
NET mRNA above and below median supine plasma DHPG:NE
Measured: 1 day
Secondary outcomes (2)
Standing Plasma DHPG:NE correlation
NET mRNA above and below median standing plasma DHPG:NE
Measured: 1 day
Urine DHPG:NE correlation
NET mRNA above and below median urine DHPG:NE
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2017
- Study start14 Jul 2017
- Primary completion31 Dec 2029 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Postural Tachycardia SyndromeStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
- Target duration
- 2 Days
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- University of Calgary, Dysautonomia International
- Responsible party
- Principal investigator, Satish R. Raj, Vanderbilt University Medical Center
- Investigators
- Satish R Raj, MD MSCI, Principal investigator, Vanderbilt University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03218761
- Sponsor's protocol ID
- IRB#170714
- Status last verified
- Oct 2026
- First submitted
- 12 Jul 2017
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Validation of Norepinephrine Transporter (NET) mRNA as a Measure of Functional NET Expression in Postural Tachycardia Syndrome (POTS)
- ClinicalTrials.gov ID
- NCT03218761
- Acronym / sponsor ID
- IRB#170714
- Conditions
- Postural Tachycardia Syndrome
- Keywords
- norepinephrine, norepinephrine transporter
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Collaborators
- University of Calgary, Dysautonomia International
- Study start
- 14 Jul 2017 (actual)
- Primary completion
- 31 Dec 2029 (estimated)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 17 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
DNA Acetylation can be responsible for significant down-regulation of transcription of the Norepinephrine Transporter (NET). NET is an important clearance transporter that removes norepinephrine (NE) from sympathetic neuronal synapses. Very low levels of NET can "cause" Postural Tachycardia Syndrome (POTS) or make these patients more susceptible to certain medications. Quantified NET messenger RNA (mRNA) levels from a peripheral blood sample may be able to assess NET availability, which is simpler than older methods. This has not been validated against NET function. In this protocol, the investigators seek to assess whether these NET mRNA levels correlate with NET function. The investigators will assess the DHPG (NET dependent NE metabolite):NE ratio in POTS patients and control subjects from both plasma and urine samples.
Detailed description
Work from The Baker Institute in Melbourne, Australia has shown that there can be significant epigenetic modification of the Norepinephrine Transporter (NET). DNA Acetylation can be responsible for significant down-regulation of transcription. NET is an important clearance transporter that removes norepinephrine (NE) from sympathetic neuronal synapses.Very low levels of NET can produce a hyperadrenergic phenotype and can "cause" Postural Tachycardia Syndrome (POTS). The Baker Institute researchers have started using quantified NET mRNA levels from a peripheral blood sample to assess NET availability. This is a huge advance due to its simplicity, in contrast to a prior method which involved a vein biopsy to look at the level of protein expression.
In this protocol, the investigators seek to assess whether these NET messenger RNA (mRNA) levels correlate with NET function. When NET transports NE back into presynaptic neurons, a high percentage gets converted to a metabolite (DHPG) and then released into the blood stream. Therefore, the ratio of DHPG:NE ratio is decreased with reduced NET activity. The investigators will assess this DHPG:NE ratio in POTS patients and control subjects from both plasma and urine samples.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 2 Days
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| POTS Patients | – | Diagnostic Test: NET mRNA level, Diagnostic Test: Plasma catechols, Diagnostic Test: Urine CatecholsPatients who self-identify as having Postural Tachycardia Syndrome. They will have assessment of NET mRNA levels, supine plasma catechols, standing plasma catechols, and urine catechols. |
| Control Subjects | – | Diagnostic Test: NET mRNA level, Diagnostic Test: Plasma catechols, Diagnostic Test: Urine CatecholsSubjects who do not have Postural Tachycardia Syndrome. They will have assessment of NET mRNA levels, supine plasma catechols, standing plasma catechols, and urine catechols. |
Who may qualify
- Ages
- 13 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients with POTS and Subjects without POTS who are not on drugs that inhibit the norepinephrine transporter and are willing to give their informed consent (or assent and parental consent) to participate in the project.
Key inclusion criteria (7 listed)
- • Postural Tachycardia Syndrome
Key exclusion criteria (6 listed)
- • Inability to give, or withdrawal of, informed consent
- o These drugs pharmacologically block NET activity
- o Many tricyclic antidepressants pharmacologically block NET activity
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NET mRNA levelquantification of mRNA to the Norepinephrine Transporter (NET) | Diagnostic test | Control Subjects, POTS Patients |
| Plasma catecholsplasma for assay of norepinephrine (NE), DHPG (intraneuronal metabolite of NE), and other catechols | Diagnostic test | Control Subjects, POTS Patients |
| Urine Catecholsurine for assay of norepinephrine (NE), DHPG (intraneuronal metabolite of NE), and other catechols | Diagnostic test | Control Subjects, POTS Patients |
Primary outcome
Supine Plasma DHPG:NE correlation
Time frame: 1 day
NET mRNA above and below median supine plasma DHPG:NE
2 secondary outcomes
Standing Plasma DHPG:NE correlation
Time frame: 1 day
Urine DHPG:NE correlation
Time frame: 1 day
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Satish R Raj, MD MSCI principal investigator
Vanderbilt University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Postural Tachycardia Syndrome, run by Vanderbilt University Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 16 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Supine Plasma DHPG:NE correlation (time frame: 1 day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2026.