POTS NET mRNA Functional Correlation With NET Activity
| Status: | Enrolling by invitation |
|---|---|
| Conditions: | Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 13 - 80 |
| Updated: | 8/12/2018 |
| Start Date: | July 14, 2017 |
| End Date: | December 31, 2021 |
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.
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.
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.
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.
Inclusion Criteria:
- • 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)
Exclusion Criteria:
- • 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.
We found this trial at
1
site
1211 Medical Center Dr
Nashville, Tennessee 37232
Nashville, Tennessee 37232
(615) 322-5000
Vanderbilt Univ Med Ctr Vanderbilt University Medical Center (VUMC) is a comprehensive healthcare facility dedicated...
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