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Modafinil and Cognitive Function in POTS

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01988883
Recruitment Status : Active, not recruiting
First Posted : November 20, 2013
Last Update Posted : January 11, 2021
Sponsor:
Information provided by (Responsible Party):
Italo Biaggioni, Vanderbilt University Medical Center

Tracking Information
First Submitted Date  ICMJE November 13, 2013
First Posted Date  ICMJE November 20, 2013
Last Update Posted Date January 11, 2021
Actual Study Start Date  ICMJE October 2014
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 13, 2013)
Visual Attention Performance Speed [ Time Frame: 2.5 hours post study medication ]
This outcome will be assessed using the CogState Identification Task which provides a continuous variable for visual attention performance speed.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 25, 2018)
  • Executive Function [ Time Frame: 2.5 hours post study medication ]
    This outcome will be assessed by the CogState Groton Maze Learning and Set-Shifting Tasks which provides continuous variables for speed and accuracy measures of executive function.
  • Blood Pressure [ Time Frame: Baseline and up to 4 hours after drug administration ]
    This outcome will be assessed using an automated sphygmomanometer arm cuff.
  • Heart Rate [ Time Frame: Baseline and up to 4 hours after drug administration ]
    This outcome will be assessed using an automated sphygmomanometer arm cuff.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 13, 2013)
Stroop Test of Executive Function [ Time Frame: 2.5 hours post study medication ]
This outcome will be assessed with the Stroop Word Color test which provides a continuous variable t-score for executive function.
Current Other Pre-specified Outcome Measures
 (submitted: September 11, 2014)
  • Processing speed [ Time Frame: 2.5 hours post study medication ]
    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 ]
    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 ]
    This outcome will be assessed by the CogState One-Back task which provides continuous variables for speed and accuracy measures of working memory.
Original Other Pre-specified Outcome Measures
 (submitted: November 13, 2013)
  • Processing speed [ Time Frame: 2.5 hours post study medication ]
    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 ]
    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 ]
    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 ]
    This outcome will be assessed by the CogState Groton Maze Learning Task which provides continuous variables for speed and accuracy measures of executive function.
 
Descriptive Information
Brief Title  ICMJE Modafinil and Cognitive Function in POTS
Official Title  ICMJE Modafinil and Cognitive Function in Postural Tachycardia Syndrome
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.

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. 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Postural Tachycardia Syndrome
Intervention  ICMJE
  • 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
  • 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
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Placebo
  • 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.
    Interventions:
    • Drug: Placebo
    • Drug: Modafinil
  • 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.
    Interventions:
    • Drug: Placebo
    • Drug: Propranolol
  • 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.
    Interventions:
    • Drug: Modafinil
    • Drug: Propranolol
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 25, 2018)
20
Original Estimated Enrollment  ICMJE
 (submitted: November 13, 2013)
47
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01988883
Other Study ID Numbers  ICMJE 131371
5UL1TR000445-07 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Italo Biaggioni, Vanderbilt University Medical Center
Study Sponsor  ICMJE Vanderbilt University Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Italo Biaggioni, M.D. Vanderbilt University Medical Center
PRS Account Vanderbilt University Medical Center
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP