NCT03218761

Brief 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. 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.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
200

participants targeted

Target at P75+ for all trials

Timeline
45mo left

Started Jul 2017

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress71%
Jul 2017Dec 2029

First Submitted

Initial submission to the registry

July 12, 2017

Completed
2 days until next milestone

Study Start

First participant enrolled

July 14, 2017

Completed
3 days until next milestone

First Posted

Study publicly available on registry

July 17, 2017

Completed
12.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2029

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2029

Last Updated

October 14, 2025

Status Verified

October 1, 2025

Enrollment Period

12.5 years

First QC Date

July 12, 2017

Last Update Submit

October 8, 2025

Conditions

Postural Tachycardia Syndrome

Keywords

norepinephrinenorepinephrine transporter

Outcome Measures

Primary Outcomes (1)

  • Supine Plasma DHPG:NE correlation

    NET mRNA above and below median supine plasma DHPG:NE

    1 day

Secondary Outcomes (2)

  • Standing Plasma DHPG:NE correlation

    1 day

  • Urine DHPG:NE correlation

    1 day

Study Arms (2)

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.

Diagnostic Test: NET mRNA levelDiagnostic Test: Plasma catecholsDiagnostic 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.

Diagnostic Test: NET mRNA levelDiagnostic Test: Plasma catecholsDiagnostic Test: Urine Catechols

Interventions

NET mRNA levelDIAGNOSTIC_TEST

quantification of mRNA to the Norepinephrine Transporter (NET)

Control SubjectsPOTS Patients
Plasma catecholsDIAGNOSTIC_TEST

plasma for assay of norepinephrine (NE), DHPG (intraneuronal metabolite of NE), and other catechols

Control SubjectsPOTS Patients
Urine CatecholsDIAGNOSTIC_TEST

urine for assay of norepinephrine (NE), DHPG (intraneuronal metabolite of NE), and other catechols

Control SubjectsPOTS Patients

Eligibility Criteria

Age13 Years - 80 Years
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
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.

You may qualify if:

  • 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)

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma samples supine and upright catechol levels Urine for catechol levels PAXgene tubes for RNA assessment plasma/serum aliquots

MeSH Terms

Conditions

Postural Orthostatic Tachycardia Syndrome

Condition Hierarchy (Ancestors)

Orthostatic IntolerancePrimary DysautonomiasAutonomic Nervous System DiseasesNervous System Diseases

Study Officials

  • Satish R Raj, MD MSCI

    Vanderbilt University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Target Duration
2 Days
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Adjunct Associate Professor of Medicine

Study Record Dates

First Submitted

July 12, 2017

First Posted

July 17, 2017

Study Start

July 14, 2017

Primary Completion (Estimated)

December 31, 2029

Study Completion (Estimated)

December 31, 2029

Last Updated

October 14, 2025

Record last verified: 2025-10

Data Sharing

IPD Sharing
Will not share

Locations

US(1)