Vagal Stimulation in POTS - The Autonomic Inflammatory Reflex (Pilot 3)

Vagal Stimulation in POTS



Sponsors


Source

Vanderbilt University Medical Center

Oversight Info

Has Dmc

No

Is Fda Regulated Drug

Yes

Is Fda Regulated Device

No

Is Us Export

No


Brief Summary

The purpose of this study is to investigate how the electrical stimulation of a nerve in the
skin of the earlobe (transcutaneous vagal nerve stimulation), alone or in combination with
two medications (galantamine and pyridostigmine), affects the way the autonomic (involuntary)
nervous system controls heart rhythm, symptoms on standing, and inflammatory markers in
female patients with postural tachycardia syndrome (POTS). The study consists of 2 parts: a
screening (1-2 study days), and 3 testing days. The study will take 5 days total and about 16
participants will be screened for the study. The investigators estimate 13 will be eligible
to participate in all of the study days.

Detailed Description

This study will test the hypothesis that impairment of the parasympathetic nervous system
contributes to the symptoms of POTS and that stimulation of this part of the nervous system
improves the excessive increase in heart rate, standing tolerance and inflammation in
patients with POTS. For this purpose, the investigators will use electrical stimulation of a
nerve in the skin of the earlobe (transcutaneous vagal nerve stimulation) and two medications
that increase the levels of acetylcholine (a neurotransmitter) in the central or peripheral
nervous system (galantamine and pyridostigmine, respectively) to increase the activity of the
parasympathetic nervous system.

Screening Procedures: Potential participants will be screened in the Vanderbilt Autonomic
Dysfunction Center (ADC). Medications affecting heart rate, blood pressure, blood volume,
inflammatory markers and the autonomic nervous system will be withdrawn for at least five
half-lives before studies. Patients will undergo a complete history and physical examination,
ECG, routine clinical laboratory analyses and a blood pregnancy test for women of
childbearing potential. Autonomic testing including a posture study with plasma
catecholamines is then performed to determine if they meet the inclusion/exclusion criteria.

Eligible participants will be studied on three separate days in a randomized, double-blind,
crossover fashion. On each testing day, patients will be given one dose of the study
medication (either pyridostigmine, galantamine or placebo pill), and then will have two tilt
table tests (a motorized table with a footboard that moves to an upright position): one with
the vagal stimulation and one with sham electrical stimulation. Heart rhythm, blood pressure
and the amount of fluid in the body (body impedance) will be monitored during studies. Blood
samples (up to a total of 2 tablespoons per study day) will also be collected. The order of
the study days and tilt tests will be decided at random, like the toss of a coin. Each study
day will last about 5 hours.

Overall Status

Recruiting

Start Date

2017-09-30

Completion Date

2020-12-01

Primary Completion Date

2020-07-01

Phase

Phase 1

Study Type

Interventional

Primary Outcome

Measure

Time Frame

High frequency variability of heart rate
Up to 15 min of head up tilt

Enrollment

16

Condition


Intervention

Intervention Type

Drug

Intervention Name


Description

placebo single oral dose

Arm Group Label

Placebo pill with vagal/sham stimulation

Other Name

placebo


Intervention Type

Drug

Intervention Name


Description

pyridostigmine bromide 30 mg single oral dose

Arm Group Label

Pyridostigmine with vagal/sham stimulation

Other Name

pyridostigmine bromide

Mestinon



Intervention Type

Drug

Intervention Name


Description

Galantamine hydrobromide 8mg single oral dose

Arm Group Label

Galantamine with vagal/sham stimulation

Other Name

Galantamine hydrobromide

Razadyne



Intervention Type

Device

Intervention Name


Description

Vagal stimulation will be given at 50 Hz during the tilt table tests

Arm Group Label

Placebo pill with vagal/sham stimulation

Pyridostigmine with vagal/sham stimulation

Galantamine with vagal/sham stimulation


Other Name

Transcutaneous vagal nerve stimulation


Intervention Type

Device

Intervention Name


Description

Sham vagal stimulation will be given at 0.01 mA during the tilt table tests

Arm Group Label

Placebo pill with vagal/sham stimulation

Pyridostigmine with vagal/sham stimulation

Galantamine with vagal/sham stimulation




Eligibility

Criteria

Inclusion Criteria:

- Female subjects of 18-45 years, with Postural Tachycardia Syndrome (POTS) as defined
by a heart rate increase ≥30 bpm from supine within 10 min of standing or head-up tilt
in the absence of orthostatic hypotension, with chronic symptoms (> 6 months), and in
the absence of other acute cause of orthostatic tachycardia.

- Subjects able and willing to provide informed consent

Exclusion Criteria:

- Pregnancy.

- Medical conditions that can explain postural tachycardia (e.g., dehydration,
medications).

- Patients who are bedridden or chair-ridden

- Subjects taking any medication known to affect autonomic function or inflammatory
markers (e.g. corticosteroids) who could not discontinue them before study
participation.

- Conditions associated with chronic inflammatory processes which in the investigator's
opinion would affect the interpretation of the results. Examples may include smoking,
diabetes, BMI>30 kg/m2, current infections or cancer.

- Other factors which in the investigator's opinion would prevent the subject from
completing the protocol.

Gender

Female

Minimum Age

18 Years

Maximum Age

45 Years

Healthy Volunteers

No


Overall Official

Last Name

Role

Affiliation

Italo Biaggioni, MD
Principal Investigator
Vanderbilt University Medical Center

Overall Contact

Last Name

Misty D Hale, CCRP

Phone

615-322-2931

Email



Location

Facility

Status

Contact

Investigator

Autonomic Dysfunction Center/ Vanderbilt University Medical Center
Nashville Tennessee 37232 United States
Recruiting
Last Name: Misty Hale, CCRP
Phone: 615-322-2931
Email: [email protected]
Last Name: Bonnie K Black, RN
Role: Sub-Investigator

Last Name: Luis E Okamoto, MD
Role: Sub-Investigator

Last Name: David Robertson, MD
Role: Sub-Investigator

Last Name: Italo Biaggioni, MD
Role: Principal Investigator

Last Name: Alfredo Gamboa, MD
Role: Sub-Investigator

Last Name: Cyndya A Shibao, MD
Role: Sub-Investigator

Last Name: Andre Diedrich, MD, PhD
Role: Sub-Investigator

Last Name: jorge Celedonio, MD
Role: Sub-Investigator


Location Countries

Country

United States


Verification Date

2017-10-01

Lastchanged Date

2017-10-13

Firstreceived Date

2017-04-18

Responsible Party

Responsible Party Type

Principal Investigator

Investigator Affiliation

Vanderbilt University Medical Center

Investigator Full Name

Italo Biaggioni

Investigator Title

Professor of Medicine and Pharmacology


Keywords


Has Expanded Access

No

Condition Browse


Number Of Arms

3

Intervention Browse

Mesh Term

Bromides

Galantamine

Pyridostigmine Bromide



Arm Group

Arm Group Label

Placebo pill with vagal/sham stimulation

Arm Group Type

Experimental

Description

Patients will receive a single oral dose of placebo sugar pill, and 1.5-2 hours later they will have two tilt table tests: one with vagal stimulation and one with sham vagal stimulation


Arm Group Label

Pyridostigmine with vagal/sham stimulation

Arm Group Type

Experimental

Description

Patients will receive a single oral dose of pyridostigmine pill 30 mg, and 1.5-2 hours later they will have two tilt table tests: one with vagal stimulation and one with sham vagal stimulation


Arm Group Label

Galantamine with vagal/sham stimulation

Arm Group Type

Experimental

Description

Patients will receive a single oral dose of galantamine pill 8 mg, and 1.5-2 hours later they will have two tilt table tests:one with vagal stimulation and one with sham vagal stimulation



Firstreceived Results Date

N/A

Overall Contact Backup

Last Name

Luis Okamoto, MD

Phone

615-936-6119

Email



Patient Data

Sharing Ipd

No


Firstreceived Results Disposition Date

N/A

Study Design Info

Allocation

Randomized

Intervention Model

Crossover Assignment

Intervention Model Description

Randomized, double-blind, crossover

Primary Purpose

Basic Science

Masking

Double (Participant, Investigator)

Masking Description

Participants and investigators will be blinded to the study drugs (placebo, galantamine, pyridostigmine). Participants will be blinded to the vagal stimulation (stimulation vs. sham).


Study First Submitted

April 18, 2017

Study First Submitted Qc

April 18, 2017

Study First Posted

April 21, 2017

Last Update Submitted

October 13, 2017

Last Update Submitted Qc

October 13, 2017

Last Update Posted

October 16, 2017


ClinicalTrials.gov processed this data on October 16, 2017

Conditions

Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov, conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.



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