Modafinil and Cognitive Function in POTS

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by Vanderbilt University
Sponsor:
Information provided by (Responsible Party):
Amy Arnold, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT01988883
First received: November 13, 2013
Last updated: NA
Last verified: November 2013
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Postural Tachycardia Syndrome
Drug: Placebo
Drug: Modafinil
Drug: Propranolol
Phase 0

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Modafinil and Cognitive Function in Postural Tachycardia Syndrome

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Visual Attention Performance Speed [ Time Frame: 2.5 hours post study medication ] [ Designated as safety issue: No ]
    This outcome will be assessed using the CogState Identification Task which provides a continuous variable for visual attention performance speed.


Secondary Outcome Measures:
  • Stroop Test of Executive Function [ Time Frame: 2.5 hours post study medication ] [ Designated as safety issue: No ]
    This outcome will be assessed with the Stroop Word Color test which provides a continuous variable t-score for executive function.


Other Outcome Measures:
  • Processing speed [ Time Frame: 2.5 hours post study medication ] [ Designated as safety issue: No ]
    This outcome will be assessed by the CogState Detection task which provides continuous variables for speed and accuracy measures of processing speed.

  • Visual learning and memory [ Time Frame: 2.5 hours post study medication ] [ Designated as safety issue: No ]
    This outcome will be assessed by the CogState One Card Learning task which provides continuous variables for speed and accuracy measures of visual learning and memory.

  • Working memory [ Time Frame: 2.5 hours post study medication ] [ Designated as safety issue: No ]
    This outcome will be assessed by the CogState One-Back task which provides continuous variables for speed and accuracy measures of working memory.

  • Groton Test of Executive function [ Time Frame: 2.5 hours post study medication ] [ Designated as safety issue: No ]
    This outcome will be assessed by the CogState Groton Maze Learning Task which provides continuous variables for speed and accuracy measures of executive function.


Estimated Enrollment: 47
Study Start Date: November 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
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
Locking gelatin capsules filled with microcrystalline cellulose
Experimental: Modafinil
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
Locking gelatin capsules filled with microcrystalline cellulose
Drug: Modafinil
Modafinil is a wakefulness-promoting or psychostimulant drug. It will be administered as a single 200 mg oral tablet.
Other Name: Provigil
Experimental: Propranolol
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
Locking gelatin capsules filled with microcrystalline cellulose
Drug: Propranolol
Propranolol is a non-selective beta adrenergic antagonist.It will be administered as a single 20 mg oral tablet.
Other Names:
  • Inderal
  • Inderal LA
  • Innopran XL
Experimental: Modafinil plus Propranolol
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
Modafinil is a wakefulness-promoting or psychostimulant drug. It will be administered as a single 200 mg oral tablet.
Other Name: Provigil
Drug: Propranolol
Propranolol is a non-selective beta adrenergic antagonist.It will be administered as a single 20 mg oral tablet.
Other Names:
  • Inderal
  • Inderal LA
  • Innopran XL

Detailed Description:

Postural Tachycardia Syndrome (POTS) is one of the most frequent forms of chronic orthostatic intolerance and affects an estimated 500,000 people in the United States alone. This disorder is a common source of disability in young adults, with a strong predilection for premenopausal women. POTS is characterized by an excessive increase in heart rate (>30 bpm) on assuming the upright position that is associated with orthostatic symptoms that are relieved by lying down. These symptoms include palpitations, chest pain, lightheadedness or dizziness, blurred vision, nausea and fatigue. In addition, POTS patients commonly report mental clouding or "brain fog" even while lying down or seated, which can pose significant limitations to daily life.

Although mental clouding is an almost universal complaint among POTS patients, this phenomenon is poorly understood. As a result, the optimal treatment strategies to manage cognitive dysfunction in this condition remain unknown. The purpose of this study is to better define the mental clouding associated with POTS and to determine whether the psychostimulant modafinil is a viable therapeutic option to improve cognitive function in these patients. The investigators hypothesize that acute modafinil administration will improve seated measures of cognitive function in POTS patients. The specific aims are:

  1. To assess whether acute modafinil improves seated measures of cognitive function, particularly measures of attention and executive function, in POTS patients compared to placebo.
  2. To assess whether propranolol, either alone as an active control or in combination with modafinil to mitigate potential heart rate increases, can improve cognitive function in POTS.

Patients will be studied on 4 separate days with oral administration of: placebo, modafinil (200 mg), propranolol (20 mg) and the combination of modafinil (200 mg) and propranolol (20 mg). The order of administration will be randomized in a double-blind manner. Patients will be seated during the study and cognitive testing will begin approximately 2.5 hours after medication administration. Cognitive testing will consist of the CogState computerized brief battery and a Stroop Word Color test of executive function. Patients will also be asked to stand for 10 minutes (or as long as tolerated) at 1, 3 and 4 hours post medication, with some of the cognitive tests repeated while standing at the 4 hour time point.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01988883

Contacts
Contact: Bonnie K Black, R.N. adcresearch@vanderbilt.edu
Contact: Cindy A Dorminy, MEd, LPN adcresearch@vanderbilt.edu

Locations
United States, Tennessee
Vanderbilt University Recruiting
Nashville, Tennessee, United States, 37211
Contact: Bonnie K Black, RN       adcresearch@vanderbilt.edu   
Principal Investigator: Amy C Arnold, Ph.D.         
Sub-Investigator: Satish R Raj, M.D.         
Sub-Investigator: Vidya Raj, M.B., Ch.B.         
Sub-Investigator: Kirsten Haman, Ph.D.         
Sub-Investigator: Italo Biaggioni, M.D.         
Sub-Investigator: David Robertson, M.D.         
Sub-Investigator: Cyndya A Shibao, M.D.         
Sub-Investigator: Emily M Garland, Ph.D.         
Sub-Investigator: Bonnie K Black, R.N.         
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Amy C Arnold, Ph.D. Vanderbilt University
  More Information

No publications provided

Responsible Party: Amy Arnold, Research Instructor, Vanderbilt University
ClinicalTrials.gov Identifier: NCT01988883     History of Changes
Other Study ID Numbers: 131371, 5UL1TR000445-07
Study First Received: November 13, 2013
Last Updated: November 13, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Vanderbilt University:
Autonomic Nervous System Diseases
Primary Dysautonomias
Postural Tachycardia Syndrome
Tachycardia
Orthostatic Intolerance
Nervous System Diseases
Cardiovascular Diseases
Modafinil
Propranolol
Neurobehavioral Manifestations
Neurologic Manifestations
Cognitive Symptoms
Neuropsychological Tests

Additional relevant MeSH terms:
Primary Dysautonomias
Autonomic Nervous System Diseases
Tachycardia
Postural Orthostatic Tachycardia Syndrome
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Orthostatic Intolerance
Nervous System Diseases
Propranolol
Modafinil
Armodafinil
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Antihypertensive Agents
Vasodilator Agents
Wakefulness-Promoting Agents
Central Nervous System Stimulants
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 21, 2014