Non-Invasive Brain Stimulation for Cyclic Vomiting Syndrome

Overseen By David J Levinthal, MD PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Pittsburgh

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

Disqualifiers: Psychosis, Seizures, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

110 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to study and understand cyclic vomiting syndrome (CVS) using Transcranial Magnetic Stimulation (TMS), a non-invasive brain stimulation technique. Researchers compare brain activity between individuals with CVS and those without to identify any differences. Individuals with CVS, who experience recurring episodes of severe vomiting, may qualify for the trial. The study aims to uncover insights that could lead to better future treatments for CVS. As an unphased trial, it offers participants the chance to contribute to groundbreaking research that could pave the way for future CVS treatments.

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 prior data suggests that this non-invasive brain stimulation method is safe?

Research has shown that non-invasive brain treatments like Transcranial Magnetic Stimulation (TMS) are generally safe. Studies have found that both repetitive TMS and a similar method, tCS, are safe for children and teenagers with various brain conditions, suggesting TMS is likely safe for adults too.

However, mild side effects can occur. Some people might experience headaches or feel slightly nauseous after TMS. In rare cases, high-frequency TMS might cause more intense headaches, but these effects are usually temporary and not serious.

One study highlighted that standard non-invasive brain treatments are well-tolerated and considered to have minimal risk, especially in children, indicating their safety in adults as well.

In summary, TMS is generally well-tolerated, with only mild and temporary side effects reported. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using non-invasive brain stimulation for Cyclic Vomiting Syndrome (CVS) because it offers a fresh approach compared to traditional treatments like anti-emetic medications, dietary changes, and lifestyle modifications. This technique uses transcranial magnetic stimulation (TMS) to assess and potentially modulate brain activity without the need for surgery or medication, which could reduce side effects. By targeting cortical excitability and autonomic activity, it could provide a more direct way to manage symptoms, offering hope for faster relief and a better quality of life for patients.

What evidence suggests that this non-invasive brain stimulation is effective for cyclic vomiting syndrome?

Research has shown that non-invasive brain treatments, such as Transcranial Magnetic Stimulation (TMS), might help adjust brain activity. TMS uses magnetic fields to stimulate brain cells and is under study for various brain-related conditions. Early results suggest it can alter brain function, potentially aiding those with cyclic vomiting syndrome (CVS), which causes severe, unexplained vomiting episodes. This trial will compare CVS subjects with healthy, non-CVS subjects to evaluate TMS's potential in managing CVS symptoms. Although specific data on CVS is limited, TMS has shown promise in altering brain functions related to similar symptoms in other conditions, suggesting it could be a new way to manage CVS symptoms. ^{1 3 6 7 8}

Who Is on the Research Team?

David J Levinthal, MD PhD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Autonomic activity
• TMS Paired-Pulse assessment of cortical excitability

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

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Cortical Excitability in Cyclic Vomiting Syndrome This exploratory study will determine if there are differences in cortical excitability between patients suffering from cyclic vomiting syndrome (CVS) and ...

2. withpower.com withpower.com/trial/phase-syndrome-3-2022-2145b

Non-Invasive Brain Stimulation for Cyclic Vomiting Syndrome This exploratory study will determine if there are differences in cortical excitability between patients suffering from cyclic vomiting syndrome (CVS) and ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11911082/

Future Applications of Central Neuromodulation and ... Non‐invasive neuromodulation strategies are increasingly being explored and include various techniques such as peripheral auricular branch of ...

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05256160/cortical-excitability-in-cyclic-vomiting-syndrome

Cortical Excitability in Cyclic Vomiting Syndrome This exploratory study will determine if there are differences in cortical excitability between patients suffering from cyclic vomiting syndrome ...

5. frontiersin.org frontiersin.org/journals/pain-research/articles/10.3389/fpain.2023.1203541/full

Percutaneous electrical nerve field stimulation improves ... Percutaneous electrical nerve field stimulation improves comorbidities in children with cyclic vomiting syndrome · Introduction: Children with cyclic vomiting ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4459719/

Safety of Noninvasive Brain Stimulation in Children and ... Our findings indicate that both repetitive TMS and tCS are safe modalities in children and adolescents with various neurological conditions.

7. brainstimjrnl.com brainstimjrnl.com/article/S1935-861X(19)30496-6/pdf

Safety and tolerability of transcranial magnetic and direct ... Conclusions: Standard non-invasive brain stimulation paradigms are safe and well- tolerated in children and should be considered minimal risk.

8. sciencedirect.com sciencedirect.com/science/article/pii/S1388245720305149

Safety and recommendations for TMS use in healthy ... At present, no significant data on safety for such multi-coil stimulation is available. ... paired-pulse TMS in pediatrics is safe for children two years and ...