Cardiovagal Baroreflex Deficits Impair Neurovascular Coupling and Cognition in POTS

Summary

Postural tachycardia syndrome (POTS), is the chronic form of orthostatic intolerance associated with excessive upright tachycardia, and occurs predominantly in young females (\>85%). Among its most troubling symptoms are lightheadedness, fatigue, and decreased memory often called "brain fog" by patients. Task-related neurovascular coupling (NVC) links neural activity to an increase in CBF known as "functional hyperemia". Although memory task performance and NVC deteriorated with angle of tilt in POTS but not healthy controls, cerebral blood flow (CBF) remained similar to control. Instead, the investigators observed extensive narrow band low frequency (0.07-0.13 Hz) oscillations in BP (OBP) that entrained and amplified oscillations in CBF (OCBF). OBP and OCBF increased with tilt angle and caused impaired working memory and reduced functional hyperemia. The cardiovagal baroreflex couples BP to HR to buffer BP changes. The investigators hypothesize that the cardiovagal baroreflex becomes progressively impaired with orthostasis in POTS, but not in healthy volunteers, and accounts for OBP, OCBF, and loss of NVC; further, improving the baroreflex reduces OBP, OCBF and Brain Fog in POTS.

Conditions

• Postural Orthostatic Tachycardia Syndrome (POTS)
• POTS
• Orthostatic Intolerance

Interventions

DRUG

Pyridostigmine

60mg by mouth

DRUG

Digoxin

0.5 (500mcg) by mouth

DRUG

Placebo

Lactulose 50mg by mouth

Sponsors & Collaborators

• National Institutes of Health (NIH)

  collaborator NIH

• New York Medical College

  lead OTHER

Principal Investigators

• Julian M. Stewart, M.D., Ph.D. · New York Medical College

Study Design

Allocation

RANDOMIZED

Purpose

DIAGNOSTIC

Masking

QUADRUPLE

Model

CROSSOVER

Eligibility

Min Age

15 Years

Max Age

30 Years

Sex

FEMALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2017-07-01

Primary Completion

2022-06-01

Completion

2022-06-01

FDA Drug

Yes

Countries

• United States

Study Locations