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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether modafinil can alleviate "brain fog" in individuals with Postural Orthostatic Tachycardia Syndrome (POTS), a condition causing rapid heart rate and dizziness upon standing. Participants will receive modafinil, propranolol (which affects heart rate), a combination of both, or a placebo to determine which best improves focus and thinking skills while seated. Ideal candidates are those diagnosed with POTS, experiencing symptoms that worsen when standing but improve when lying down, and not taking certain medications like SNRIs. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants a chance to contribute to groundbreaking insights.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that modafinil is generally safe for people with Postural Orthostatic Tachycardia Syndrome (POTS). One study found that modafinil did not significantly increase heart rate when standing or cause sudden symptoms compared to a placebo. In fact, it even helped improve blood pressure when standing.

Caution is advised when combining modafinil with propranolol. While modafinil may help with symptoms, it can sometimes raise heart rate. However, studies suggest it does not significantly worsen symptoms related to standing.

Overall, modafinil has shown positive effects in treating POTS symptoms like tiredness and "brain fog." However, since this trial is in the early stages, detailed safety results specific to this study are not yet available. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for Postural Orthostatic Tachycardia Syndrome (POTS) typically involve medications like beta-blockers (e.g., propranolol) and fludrocortisone, which help manage heart rate and blood volume. However, modafinil stands out because it is a wakefulness-promoting agent that targets the brain's neurotransmitters, potentially improving alertness and reducing fatigue, which are common symptoms for POTS patients. Researchers are excited about modafinil's unique mechanism of action, as it might offer benefits beyond the cardiovascular focus of standard treatments. Additionally, when combined with propranolol, modafinil may enhance overall symptom control, providing a more holistic approach to managing POTS.

What evidence suggests that this trial's treatments could be effective for POTS?

Research has shown that modafinil might help with "brain fog" in people with POTS. In a study of 708 children with POTS, about 68.8% reported feeling less tired and having better thinking skills when taking modafinil. Another study found that modafinil did not worsen heart rate or symptoms when standing and even helped improve blood pressure while upright. In this trial, participants may receive modafinil alone or combined with propranolol to evaluate its effectiveness further. These results suggest modafinil could be a good option for addressing thinking problems in POTS. However, more research is needed to confirm these benefits. ^{1 2 6 7 8}

Who Is on the Research Team?

Italo Biaggioni, M.D.

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4239166/

Hemodynamic Profiles and Tolerability of Modafinil in the ... Modafinil did not significantly worsen standing HR or acute orthostatic symptoms in POTS patients compared to placebo, and improved upright blood pressure.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01988883

NCT01988883 | Modafinil and Cognitive Function in POTS In this study, the investigators will test the hypothesis that acute administration of the psychostimulant drug modafinil can improve seated measures of ...

3. ahajournals.org ahajournals.org/doi/10.1161/JAHA.123.033485

Long‐Term POTS Outcomes Survey: Diagnosis, Therapy ... The LT‐POTS (Long Term POTS Outcomes Survey) included questions about quality of life, symptoms, therapies, education, employment, and social impact of disease.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1050173825000933

The evidence for treatments for postural orthostatic ... In this systematic review, we evaluate the evidence for different treatments for POTS from 21 randomized clinical trials with 750 patients that took place ...

5. withpower.com withpower.com/trial/modafinil-for-postural-orthostatic-tachycardia-syndrome-pots-16a08

Modafinil for Postural Orthostatic Tachycardia Syndrome ... In a study of 708 pediatric patients with postural orthostatic tachycardia syndrome, 68.8% showed clinical improvement in fatigue and cognitive dysfunction ...

6. mdpi.com mdpi.com/2571-841X/7/2/36

Postural Orthostatic Tachycardia Syndrome (POTS) as an ... After the patient's POTS diagnosis, Modafinil was prescribed and resolved the patient's POTS symptoms. Table 1. Vital signs recorded during ...

7. ccjm.org ccjm.org/content/86/5/333

Evaluating and managing postural tachycardia syndrome Modafinil, a psychostimulant, may improve POTS-associated cognitive symptoms. It also raises upright blood pressure without significantly ...

8. health.utoledo.edu health.utoledo.edu/clinics/hvc/syncope-center/pdfs/Modafinil.pdf

Modafinil Improves Fatigue in Patients With Orthostatic ... Thirty-six patients continued to demonstrate symptom relief from fatigue for more than 6 months. In a selective group of patients of. Ol, modafinil may improve ...