NCT03218761

POTS NET mRNA Functional Correlation With NET Activity

Validation of Norepinephrine Transporter (NET) mRNA as a Measure of Functional NET Expression in Postural Tachycardia Syndrome (POTS)

• Status: Active Not Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 200 (estimated)
• Sponsor: Vanderbilt University Medical Center · Academic / Other
• Sex: All
• Age: 13 Years – 80 Years
• Healthy volunteers: Accepted

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.

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

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	NET mRNA level	quantification of mRNA to the Norepinephrine Transporter (NET)
DIAGNOSTIC_TEST	Plasma catechols	plasma for assay of norepinephrine (NE), DHPG (intraneuronal metabolite of NE), and other catechols
DIAGNOSTIC_TEST	Urine Catechols	urine for assay of norepinephrine (NE), DHPG (intraneuronal metabolite of NE), and other catechols

Timeline

• Start date: 2017-07-14
• Primary completion: 2029-12-31
• Completion: 2029-12-31
• First posted: 2017-07-17
• Last updated: 2025-10-14

Locations

1 site across 1 country: United States