Modafinil for Postural Orthostatic Tachycardia Syndrome (POTS)

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Vanderbilt University Medical Center

Must not be taking: SNRIs, NET inhibitors

Disqualifiers: Pregnancy, Asthma, others

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 4 days

20 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications for the trial?

The trial requires that you do not take serotonin-norepinephrine reuptake inhibitors (SNRIs) or norepinephrine transporter (NET) inhibitors. If you are on these medications, you would need to stop them to participate.

Is the drug modafinil effective for treating postural orthostatic tachycardia syndrome (POTS)?

Research suggests that modafinil might help improve cognitive symptoms in POTS, but it could also worsen heart rate issues. While it may help with brain fog, its effect on heart rate needs careful consideration. ^{1 2 3 4 5}

Is modafinil safe for people with POTS?

Modafinil might stimulate the sympathetic nervous system, which could worsen heart rate issues in people with POTS, but the study did not provide specific safety outcomes for modafinil in this context. ^{1 2 6 7 8}

How does the drug modafinil differ from other treatments for POTS?

Modafinil is unique in its potential to improve cognitive symptoms associated with POTS, such as 'brain fog', but it may also stimulate the nervous system and worsen heart rate issues, unlike other treatments that primarily focus on reducing heart rate or increasing blood volume. ^{1 2 7 9 10}

Research Team

Italo Biaggioni, M.D.

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

This trial is for people aged 18-60 diagnosed with POTS by the Vanderbilt Autonomic Dysfunction Center. Participants must be able to consent and not have allergies to study meds, be pregnant or breastfeeding, dehydrated, bedridden, taking certain antidepressants (SNRIs/NET inhibitors), or have asthma due to propranolol's risks.

Inclusion Criteria

Able and willing to provide informed consent

You have been diagnosed with POTS by a specific medical center using specific criteria.

Exclusion Criteria

Pregnancy or breast-feeding

Other factors which in the investigator's opinion would prevent the subject from completing the study protocol

You have asthma because the study drug propranolol is not safe for people with asthma.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive single doses of modafinil, propranolol, and placebo on separate randomized study days, with cognitive testing conducted post-medication

4 days

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

Treatment Details

Interventions

• Modafinil

Trial Overview The study aims to see if modafinil can improve 'brain fog' in POTS patients. It involves comparing the effects of modafinil and a placebo on cognitive function when seated. Propranolol is also being tested as part of the treatment strategy.

Participant Groups

Group I: Propranolol Experimental Treatment 2 Interventions

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.

Group II: Modafinil plus Propranolol Experimental Treatment 2 Interventions

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.

Group III: Modafinil Experimental Treatment 2 Interventions

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.

Group IV: Placebo Placebo Group 1 Intervention

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.

Modafinil is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Provigil for:

• Narcolepsy
• Shift Work Sleep Disorder
• Obstructive Sleep Apnea

Approved in European Union as Modafinil for:

• Excessive daytime sleepiness associated with narcolepsy
• Shift work sleep disorder
• Obstructive sleep apnea

Approved in Canada as Alertec for:

• Narcolepsy
• Shift Work Sleep Disorder
• Obstructive Sleep Apnea

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

National Center for Advancing Translational Sciences (NCATS)

Collaborator

Trials

394

Recruited

404,000+

Findings from Research

In a study involving 54 patients with POTS, low-dose propranolol (20 mg) significantly reduced heart rates and improved symptoms compared to placebo, indicating its efficacy as a treatment option.

Higher doses of propranolol (80 mg) resulted in greater reductions in heart rate but did not provide additional symptom relief and may have worsened symptoms, suggesting that lower doses may be more beneficial for managing POTS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propranolol decreases tachycardia and improves symptoms in the postural tachycardia syndrome: less is more. Raj, SR., Black, BK., Biaggioni, I., et al.[2021]

In a study of 708 pediatric patients with postural orthostatic tachycardia syndrome, 68.8% showed clinical improvement in fatigue and cognitive dysfunction after medication treatment, indicating that medications can be effective for these symptoms.

The effectiveness of individual medications varied significantly, with methylphenidate showing a 53.1% improvement rate, while atomoxetine had only a 16.5% improvement rate, suggesting that multiple trials of different medications may be necessary to find an effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy for fatigue and cognitive dysfunction in postural orthostatic tachycardia syndrome. Boris, JR., Bernadzikowski, T.[2019]

In a study of 708 patients with postural orthostatic tachycardia syndrome, various medications were found to effectively manage symptoms, with success rates of 52.2% for light-headedness and 53.4% for pain.

The study highlighted that while insomnia treatment was more effective in females, other symptom therapies showed no gender differences, indicating that medications can be tailored to individual symptoms for better management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utilisation of medications to reduce symptoms in children with postural orthostatic tachycardia syndrome. Boris, JR., Bernadzikowski, T.[2019]

In a retrospective case series of 20 POTS patients treated with ivabradine, 60% reported symptomatic improvement, particularly in tachycardia and fatigue, suggesting potential efficacy for this treatment.

Despite the positive outcomes, some patients discontinued ivabradine due to lack of efficacy or side effects, highlighting the need for further randomized controlled trials to better assess its effectiveness in POTS patients who do not respond to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single centre experience of ivabradine in postural orthostatic tachycardia syndrome. McDonald, C., Frith, J., Newton, JL.[2021]

Postural orthostatic tachycardia syndrome (POTS) is defined by a significant increase in heart rate upon standing, specifically over 30 beats per minute in adults and over 40 beats per minute in adolescents, without the presence of other conditions that could cause tachycardia.

The recognition of POTS as a distinct clinical condition has improved, allowing for better understanding of its causes, effects, and management strategies, as illustrated by the two case studies presented.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postural orthostatic tachycardia syndrome (POTS). Sidhu, B., Obiechina, N., Rattu, N., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Hemodynamic profiles and tolerability of modafinil in the treatment of postural tachycardia syndrome: a randomized, placebo-controlled trial. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Propranolol decreases tachycardia and improves symptoms in the postural tachycardia syndrome: less is more. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Therapy for fatigue and cognitive dysfunction in postural orthostatic tachycardia syndrome. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Utilisation of medications to reduce symptoms in children with postural orthostatic tachycardia syndrome. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Single centre experience of ivabradine in postural orthostatic tachycardia syndrome. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Melatonin reduces tachycardia in postural tachycardia syndrome: a randomized, crossover trial. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Efficacy of Propranolol, Bisoprolol, and Pyridostigmine for Postural Tachycardia Syndrome: a Randomized Clinical Trial. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Postural orthostatic tachycardia syndrome (POTS). [2021]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for postural tachycardia syndrome. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Droxidopa in the Treatment of Postural Orthostatic Tachycardia Syndrome. [2017]