Non-Invasive Brain Stimulation for Cyclic Vomiting Syndrome

Recruiting in Palo Alto (17 mi)

Overseen by David J Levinthal, MD PhD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University of Pittsburgh

Must not be taking: Clozaril, Thorazine, Amphetamines, others

Disqualifiers: Psychosis, Seizures, Pregnancy, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This exploratory study will determine if there are differences in cortical excitability between patients suffering from cyclic vomiting syndrome (CVS) and healthy control subjects, as assessed by a non-invasive method of brain stimulation (Transcranial Magnetic Stimulation, TMS).

Will I have to stop taking my current medications?

You may need to stop taking certain medications that lower the seizure threshold, like clozapine, chlorpromazine, amphetamines, and some recreational drugs. The trial does not specify other medications, so check with the study team about your specific situation.

What data supports the effectiveness of the treatment for Cyclic Vomiting Syndrome?

Research suggests that Cyclic Vomiting Syndrome (CVS) involves altered brain connectivity and autonomic nervous system function, similar to migraines. Non-invasive brain stimulation, like TMS (transcranial magnetic stimulation), which targets brain areas involved in these processes, has shown promise in treating migraines, indicating potential effectiveness for CVS. ^{1 2 3 4 5}

Is non-invasive brain stimulation safe for humans?

Transcranial magnetic stimulation (TMS) is generally safe, but it can cause mild side effects like headaches and nausea. High-frequency TMS can sometimes lead to seizures, and low-frequency TMS may cause nausea, especially when applied to certain brain areas. ^{6 7 8 9 10}

How does non-invasive brain stimulation differ from other treatments for cyclic vomiting syndrome?

Non-invasive brain stimulation for cyclic vomiting syndrome is unique because it targets brain connectivity and autonomic nervous system regulation, which are linked to the condition's symptoms. Unlike traditional treatments that may focus on gastrointestinal symptoms, this approach aims to modulate brain activity and improve autonomic function, potentially addressing the root cause of the syndrome. ^{1 4 5 11 12}

Research Team

David J Levinthal, MD PhD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

This trial is for individuals diagnosed with cyclic vomiting syndrome (CVS). It's not open to those who have a history of head injury, metal in the skull, stroke, seizures, or use certain drugs like clozapine or amphetamines. Pregnant women and people with psychosis or cognitive issues can't join either.

Inclusion Criteria

I have been diagnosed with cyclic vomiting syndrome (CVS).

Exclusion Criteria

I have a history of head injury, stroke, seizures, or metal in my skull.

I am not using drugs or alcohol that increase my risk of seizures.

Pregnancy

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo Transcranial Magnetic Stimulation (TMS) to assess cortical excitability

12 months

Multiple study sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Autonomic activity (Behavioural Intervention)
• TMS Paired-Pulse assessment of cortical excitability (Procedure)

Trial Overview The study is testing how the brain's electrical activity differs between CVS patients and healthy people using Transcranial Magnetic Stimulation (TMS), which is a non-invasive brain stimulation technique.

Participant Groups

Group I: CVS subjects Experimental Treatment 2 Interventions

Subjects diagnosed with Cyclic Vomiting Syndrome (CVS)

Group II: healthy, non-CVS subjects Active Control 2 Interventions

Subjects not diagnosed with CVS

Who Is Running the Clinical Trial?

University of Pittsburgh

Lead Sponsor

Trials

1,820

Recruited

16,360,000+

David Apelian

University of Pittsburgh

Chief Executive Officer since 2019

PhD in Molecular Biology from Rutgers University, MD from the University of Medicine and Dentistry of New Jersey, MBA from Quinnipiac University

Pamela D. Garzone

University of Pittsburgh

Chief Medical Officer

PhD in Clinical Science from the University of Pittsburgh

Findings from Research

In a study of 14 pediatric patients with cyclic vomiting syndrome (CVS), it was found that these patients exhibit significantly increased sympathetic modulation of heart rate compared to healthy controls, indicating an autonomic imbalance.

The analysis revealed a low-frequency to high-frequency heart rate variability ratio of 1.45 in CVS patients versus 0.89 in healthy controls, suggesting that CVS is associated with heightened sympathetic activity and reduced parasympathetic activity in the heart.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of neurocardiac signals in pediatric patients with cyclic vomiting syndrome through power spectral analysis of heart rate variability. To, J., Issenman, RM., Kamath, MV.[2019]

Cyclic vomiting syndrome (CVS) shows distinct autonomic abnormalities, particularly a low postural adjustment ratio, which is similar to the patterns observed in patients with migraine headaches, suggesting a shared underlying mechanism.

In a study involving 88 participants across five groups, CVS patients exhibited lower cholinergic function compared to normal controls, which may aid in the diagnosis and understanding of CVS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autonomic function in cyclic vomiting syndrome and classic migraine. Rashed, H., Abell, TL., Familoni, BO., et al.[2022]

Cyclic Vomiting Syndrome (CVS) is a complex condition often misdiagnosed due to its episodic nature and lack of specific tests, affecting mainly young children but also infants and the elderly.

Management of CVS requires personalized treatment strategies, including supportive care during acute episodes and preventive measures like lifestyle changes, with pharmacotherapy considered based on the severity and impact on quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyclic Vomiting Syndrome in Children. Raucci, U., Borrelli, O., Di Nardo, G., et al.[2020]

Children with cyclic vomiting syndrome (CVS) exhibit significantly reduced cardiac vagal regulation compared to healthy controls, as indicated by shorter heart periods and lower respiratory sinus arrhythmia (RSA), suggesting altered autonomic nervous system function.

The study found that children with CVS had lower vagal efficiency during posture changes, which may provide insights into the underlying mechanisms of CVS and inform potential therapeutic strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac Vagal Regulation Is Impeded in Children With Cyclic Vomiting Syndrome. Kolacz, J., Kovacic, K., Dang, L., et al.[2023]

Cyclic Vomiting Syndrome (CVS) exhibits increased connectivity in the salience network to the middle/posterior insula, a brain area associated with nausea, compared to migraine patients and healthy controls, indicating a unique brain mechanism in CVS.

Both CVS and migraine show reduced connectivity in the sensorimotor network, suggesting shared pathophysiological features between the two conditions, which could inform future therapeutic targets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyclic Vomiting Syndrome is characterized by altered functional brain connectivity of the insular cortex: A cross-comparison with migraine and healthy adults. Ellingsen, DM., Garcia, RG., Lee, J., et al.[2018]

In a study involving eight right-handed volunteers, low-frequency repetitive transcranial magnetic stimulation (rTMS) at 0.9 Hz on the right cerebellum induced nausea in two subjects, lasting up to 10 minutes after the procedure.

Despite the nausea experienced, the study concluded that low-frequency rTMS remains a safe procedure, although researchers should be aware of this potential side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nausea as a complication of low-frequency repetitive transcranial magnetic stimulation of the posterior fossa. Satow, T., Mima, T., Hara, H., et al.[2019]

In a study involving 33 participants with bulimic disorder, a single session of high frequency repetitive Transcranial Magnetic Stimulation (rTMS) did not show any significant effects on selective attention as measured by the Stroop task.

The results indicated no difference in attention interference scores between the real rTMS and sham treatment groups, suggesting that this intervention may not impact selective attention in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immediate cognitive effects of repetitive Transcranial Magnetic Stimulation in eating disorders: a pilot study. Van den Eynde, F., Claudino, AM., Campbell, IC., et al.[2021]

In a study of 27 interictal migraineurs and 33 healthy controls, it was found that cortical inhibition was significantly decreased in migraineurs, particularly among females, suggesting a potential mechanism underlying migraine attacks.

The study also indicated that intracortical facilitation was reduced in individuals just before a migraine attack, highlighting the importance of monitoring cortical excitability in understanding and potentially predicting migraine episodes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced motor cortical inhibition in migraine: A blinded transcranial magnetic stimulation study. Neverdahl, JP., Omland, PM., Uglem, M., et al.[2018]

Mild adverse effects (MAEs) from transcranial magnetic stimulation (TMS) occur in about 5% of sessions, with most symptoms like headache and nausea reported after the sessions, particularly during initial treatments.

The study found no significant links between participant characteristics (age and gender) or TMS parameters (frequency and intensity) and the occurrence of MAEs, suggesting that initial participant anxiety may play a role in these reports.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative incidence rates of mild adverse effects to transcranial magnetic stimulation. Maizey, L., Allen, CP., Dervinis, M., et al.[2022]

Cerebellar high-frequency repetitive transcranial magnetic stimulation (rTMS) significantly increased the excitability of the bilateral cerebral cortex related to swallowing, indicating its potential effectiveness in enhancing swallowing function.

Functional MRI results showed that rTMS enhanced neural activity in key areas of the brain involved in swallowing, such as the pons and medulla, suggesting that this technique could be beneficial for clinical applications in swallowing disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Repetitive Transcranial Magnetic Stimulation of Cerebellar Swallowing Cortex on Brain Neural Activities: A Resting-State fMRI Study. Dong, L., Ma, W., Wang, Q., et al.[2022]

A novel noninvasive gastric mapping device (BSGM) was used to study 43 patients with chronic nausea and vomiting syndromes (NVS) and found that meal responses were significantly impaired in these patients compared to healthy controls, indicating potential gastric motor dysfunction.

The study identified two distinct subgroups of NVS patients based on BSGM results, with one subgroup showing abnormal gastric function correlating with specific symptoms, suggesting that personalized treatment approaches may be necessary for effective management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastric dysfunction in patients with chronic nausea and vomiting syndromes defined by a noninvasive gastric mapping device. Gharibans, AA., Calder, S., Varghese, C., et al.[2023]

The study found that increased sympathetic activity and decreased parasympathetic activity during nausea are linked to specific brain responses, indicating a complex relationship between autonomic nervous system (ANS) responses and brain activity.

The results suggest that understanding the central control of autonomic outflow could be crucial for managing nausea, highlighting the potential for targeting these mechanisms in future therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain Circuitry Supporting Multi-Organ Autonomic Outflow in Response to Nausea. Sclocco, R., Kim, J., Garcia, RG., et al.[2021]

References

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

Evaluation of neurocardiac signals in pediatric patients with cyclic vomiting syndrome through power spectral analysis of heart rate variability. [2019]

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

Autonomic function in cyclic vomiting syndrome and classic migraine. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Cyclic Vomiting Syndrome in Children. [2020]

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

Cardiac Vagal Regulation Is Impeded in Children With Cyclic Vomiting Syndrome. [2023]

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

Cyclic Vomiting Syndrome is characterized by altered functional brain connectivity of the insular cortex: A cross-comparison with migraine and healthy adults. [2018]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Nausea as a complication of low-frequency repetitive transcranial magnetic stimulation of the posterior fossa. [2019]

7. Germany pubmed.ncbi.nlm.nih.gov

Immediate cognitive effects of repetitive Transcranial Magnetic Stimulation in eating disorders: a pilot study. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Reduced motor cortical inhibition in migraine: A blinded transcranial magnetic stimulation study. [2018]

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

Comparative incidence rates of mild adverse effects to transcranial magnetic stimulation. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

The Effect of Repetitive Transcranial Magnetic Stimulation of Cerebellar Swallowing Cortex on Brain Neural Activities: A Resting-State fMRI Study. [2022]

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

Gastric dysfunction in patients with chronic nausea and vomiting syndromes defined by a noninvasive gastric mapping device. [2023]

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

Brain Circuitry Supporting Multi-Organ Autonomic Outflow in Response to Nausea. [2021]