Postural Tachycardia SyndromeEarly Phase 1NCT01988883
Modafinil and Cognitive Function in POTS
A Early Phase 1 study testing Modafinil and Propranolol in people with Postural Tachycardia Syndrome, run by Vanderbilt University Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Postural Tachycardia Syndrome
- What is being tested?
- Modafinil and Propranolol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2014to Dec 2026
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Modafinil and Cognitive Function in Postural Tachycardia Syndrome
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.
Read the 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:
- To assess whether acute modafinil improves seated measures of cognitive function, particularly measures of attention and executive function, in POTS patients compared to placebo.
- 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.
- Conditions
- Postural Tachycardia Syndrome
- Being tested
- Placebo, Modafinil, Propranolol
- 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
- Medical subject headings
- Postural Orthostatic Tachycardia Syndrome, Tachycardia, Orthostatic Intolerance, Autonomic Nervous System Diseases, Primary Dysautonomias, Nervous System Diseases, Cardiovascular Diseases, Neurobehavioral Manifestations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Locking gelatin capsules filled with microcrystalline cellulose
ModafinilDrug
Also called Provigil
Modafinil is a wakefulness-promoting or psychostimulant drug. It will be administered as a single 200 mg oral tablet.
PropranololDrug
Also called Inderal, Inderal LA, Innopran XL
Propranolol is a non-selective beta adrenergic antagonist.It will be administered as a single 20 mg oral tablet.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Modafinil; Drug: Propranolol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Visual Attention Performance Speed
This outcome will be assessed using the CogState Identification Task which provides a continuous variable for visual attention performance speed.
Measured: 2.5 hours post study medication
Secondary outcomes (3)
Executive Function
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.
Measured: 2.5 hours post study medication
Blood Pressure
This outcome will be assessed using an automated sphygmomanometer arm cuff.
Measured: Baseline and up to 4 hours after drug administration
Heart Rate
This outcome will be assessed using an automated sphygmomanometer arm cuff.
Measured: Baseline and up to 4 hours after drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2013 (estimated)
- Study startOct 2014
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Postural Tachycardia SyndromeStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Center for Advancing Translational Sciences (NCATS)
- Responsible party
- Principal investigator, Italo Biaggioni, Vanderbilt University Medical Center
- Investigators
- Italo Biaggioni, M.D., Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01988883
- Sponsor's protocol ID
- 131371
- Other IDs
- 5UL1TR000445-07
- Status last verified
- Jan 2026
- First submitted
- 13 Nov 2013
- Last updated
- 15 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modafinil and Cognitive Function in Postural Tachycardia Syndrome
- ClinicalTrials.gov ID
- NCT01988883
- Acronym / sponsor ID
- 131371
- Conditions
- Postural Tachycardia Syndrome
- Keywords
- Postural Tachycardia Syndrome, Tachycardia, Orthostatic Intolerance, Autonomic Nervous System Diseases, Primary Dysautonomias, Nervous System Diseases, Cardiovascular Diseases, Modafinil
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Collaborators
- National Center for Advancing Translational Sciences (NCATS)
- Study start
- Oct 2014 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 20 Nov 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To assess whether acute modafinil improves seated measures of cognitive function, particularly measures of attention and executive function, in POTS patients compared to placebo.
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboPatients 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. |
| Modafinil | Experimental | Drug: Placebo, Drug: ModafinilPatients 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. |
| Propranolol | Experimental | Drug: Placebo, Drug: PropranololPatients 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. |
| Modafinil plus Propranolol | Experimental | Drug: Modafinil, Drug: PropranololPatients 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboLocking gelatin capsules filled with microcrystalline cellulose | Drug | Modafinil, Placebo, Propranolol |
| ModafinilAlso: ProvigilModafinil is a wakefulness-promoting or psychostimulant drug. It will be administered as a single 200 mg oral tablet. | Drug | Modafinil, Modafinil plus Propranolol |
| PropranololAlso: Inderal, Inderal LA, Innopran XLPropranolol is a non-selective beta adrenergic antagonist.It will be administered as a single 20 mg oral tablet. | Drug | Modafinil plus Propranolol, Propranolol |
Primary outcome
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.
3 secondary outcomes
Executive Function
Time frame: 2.5 hours post study medication
Blood Pressure
Time frame: Baseline and up to 4 hours after drug administration
Heart Rate
Time frame: Baseline and up to 4 hours after drug administration
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Italo Biaggioni, M.D. principal investigator
Vanderbilt University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Modafinil and Propranolol in people with Postural Tachycardia Syndrome, run by Vanderbilt University Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 15 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Visual Attention Performance Speed (time frame: 2.5 hours post study medication). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jan 2026.