Modafinil and Cognitive Function in POTS

NCT01988883 | Active Not Recruiting Early Phase 1 FDA Drug

• 2 other identifiers: 1313715UL1TR000445-07
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

A common complaint among patients with Postural Tachycardia Syndrome (POTS) is "brain fog" or difficulty concentrating. This problem is poorly understood. The purpose of this study is to better understand the cognitive dysfunction associated POTS, and to determine optimal treatment strategies for this condition. In this study, the investigators will test the hypothesis that acute administration of the psychostimulant drug modafinil can improve seated measures of cognitive function in patients with POTS.

Conditions

Postural Tachycardia Syndrome

Keywords

Postural Tachycardia Syndrome; Tachycardia; Orthostatic Intolerance; Autonomic Nervous System Diseases; Primary Dysautonomias; Nervous System Diseases; Cardiovascular Diseases; Modafinil; Propranolol; Neurobehavioral Manifestations; Neurologic Manifestations; Cognitive Symptoms; Neuropsychological Tests

Outcome Measures

Primary Outcomes (1)

• Visual Attention Performance Speed

  This outcome will be assessed using the CogState Identification Task which provides a continuous variable for visual attention performance speed.

  2.5 hours post study medication

Secondary Outcomes (3)

• Executive Function

  2.5 hours post study medication

• Blood Pressure

  Baseline and up to 4 hours after drug administration

• Heart Rate

  Baseline and up to 4 hours after drug administration

Other Outcomes (3)

• Processing speed

  2.5 hours post study medication

• Visual learning and memory

  2.5 hours post study medication

• Working memory

  2.5 hours post study medication

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Patients will receive two inactive placebo pills filled with microcrystalline cellulose on a randomized study day. Medications will be dummy blinded to the patient and investigators.

Drug: Placebo

Modafinil

EXPERIMENTAL

Patients will receive single doses of modafinil (200 mg, oral) and placebo on a randomized study day. Medications will be dummy blinded to the patient and investigators.

Drug: Placebo; Drug: Modafinil

Propranolol

EXPERIMENTAL

Patients will receive single doses of propranolol (20 mg, oral) and placebo on a randomized study day. Medications will be dummy blinded to the patient and investigators.

Drug: Placebo; Drug: Propranolol

Modafinil plus Propranolol

EXPERIMENTAL

Patients will receive single doses of modafinil (200 mg, oral) and propranolol (20 mg, oral) on a randomized study day. Medications will be dummy blinded to the patient and investigators.

Drug: Modafinil; Drug: Propranolol

Interventions

Placebo DRUG

Locking gelatin capsules filled with microcrystalline cellulose

Modafinil; Placebo; Propranolol

Modafinil DRUG

Modafinil is a wakefulness-promoting or psychostimulant drug. It will be administered as a single 200 mg oral tablet.

Also known as: Provigil

Modafinil; Modafinil plus Propranolol

Propranolol DRUG

Propranolol is a non-selective beta adrenergic antagonist.It will be administered as a single 20 mg oral tablet.

Also known as: Inderal, Inderal LA, Innopran XL

Modafinil plus Propranolol; Propranolol

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Males and females of all races between the ages of 18 to 60 years
• Diagnosed with POTS by the Vanderbilt Autonomic Dysfunction Center based on the following consensus criteria:(a) an increase in heart rate ≥ 30 beats per minute within 10 minutes of changing from the supine to standing position; (b) absence of orthostatic hypotension (defined as a decrease in systolic blood pressure ≥ 20 mmHg or diastolic blood pressure ≥ 10 mmHg upon standing); and (c) chronic symptoms (≥ 6 months) consistent with POTS that are worse with standing and are relieved by lying down
• Able and willing to provide informed consent

You may not qualify if:

• Overt causes for POTS such as acute dehydration and bed rest deconditioning
• Patients taking serotonin-norepinephrine reuptake inhibitors (SNRIs) or norepinephrine transporter (NET) inhibitors
• Known allergies or contraindications to study medications
• Pregnancy or breast-feeding
• Inability to give or withdraw informed consent
• Other factors which in the investigator's opinion would prevent the subject from completing the study protocol such as poor compliance during previous studies
• Asthma (due to the contraindication of propranolol for asthma patients)

Sponsors & Collaborators

• National Center for Advancing Translational Sciences (NCATS): collaborator
• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University

Nashville, Tennessee, 37211, United States

Location

MeSH Terms

Conditions

Postural Orthostatic Tachycardia Syndrome; Tachycardia; Orthostatic Intolerance; Autonomic Nervous System Diseases; Primary Dysautonomias; Nervous System Diseases; Cardiovascular Diseases; Neurobehavioral Manifestations; Neurologic Manifestations

Interventions

Modafinil; Propranolol; propranolol CR

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiac Conduction System Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Italo Biaggioni, M.D.

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 13, 2013
• First Posted: November 20, 2013
• Study Start: October 1, 2014
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 15, 2026

Record last verified: 2026-01

Locations

US (1)