Clinical trial NCT05961995: Heartfulness Meditation (HFM) in Cyclic Vomiting Syndrome (CVS)
Official title: Acute and Long-term Effects of App-delivered Heartfulness Meditation on Psychological Outcomes and the Endocannabinoid Signaling System in Cyclic Vomiting Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cyclic Vomiting Syndrome
Lead sponsor: Ohio State University
Sponsor class: OTHER
First posted: 2023-07-27
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: Cyclic vomiting syndrome (CVS) is a chronic disorder of gut-brain interaction (DGBI) characterized by episodes of vomiting often triggered by stress. CVS affects 2% of the population and has a disproportionate negative impact on patients and the healthcare system. Although gastrointestinal symptoms are prominent, most patients have comorbid anxiety, depression, high degrees of psychological distress, and other negative cognitive traits that adversely affect health-related quality of life (HRQoL). This is independent of typical measures of severity of CVS and warrants treatment. Recent guidelines recommend a biopsychosocial model of care incorporating techniques like meditation to mitigate stress and improve psychological outcomes in CVS. One potential approach to improve these outcomes is the use of heartfulness (HFN) meditation.

Heartfulness meditation is a secular, specific, guided meditation technique that includes progressive relaxation with a concentrated focus on the heart. It is offered virtually and is free-of charge ensuring no barriers to broad application in clinical practice. A pilot study incorporating HFN meditation in CVS significantly reduced psychological distress, perceived stress, and improved coping strategies, sleep quality, and HRQoL. Other data also show that HFN meditation improves overall well-being and reduces perceived stress. However, there are significant gaps in our understanding of the mechanism underlying HFN meditation and its effects on patient outcomes.

The endocannabinoid signaling system (ECSS) is activated by stress exposure and functions through multiple neuroendocrine responses to mitigate the negative effects of stress. We examined the role of the ECSS in CVS and found that endocannabinoids were not elevated during an acute CVS episode. This lack of a response in the ECSS during an acute CVS episode, which is characterized by panic, intense nausea and vomiting is striking, given that the ECSS is typically activated by stress exposure. This may reflect an underlying dysfunction of the ECSS in CVS and impaired stress responsivity. Given these data and our preliminary findings of the beneficial effects of HFN meditation, our central hypothesis is that HFN meditation will increase circulating endocannabinoids in CVS and that this will be correlated with a reduction in anxiety and other psychological outcomes and overall quality of life.

We propose to test our hypothesis with the following specific aims

Specific Aim 1a: Conduct a prospective study to elucidate the acute effects of HFN meditation on the ECSS in CVS. We will measure circulating endocannabinoids and related lipids immediately before and after HFN meditation.

1b: Correlate indices of ECSS with state anxiety and mood pre-and post-HFN meditation. We will measure state anxiety and mood with validated tools including the State Trait Anxiety Inventory (STAI) and Profile of Mood States (POMS) which evaluates tension, depression, anger, vigor, fatigue, and confusion.

Hypothesis: HFN meditation will acutely increase circulating endocannabinoids which will be correlated with a reduction in state anxiety and improvement in mood.

Specific Aim 2: Determine the long-term effects of a 6-week HFN meditation program on ECSS and correlate with psychological outcomes including psychological distress, STAI scores, sleep quality, and HRQoL. We will measure these outcomes with validated tools including the Brief Symptom Inventory (BSI), STAI, Pittsburgh Sleep Quality Index (PSQI), and PROMIS quality of life questionnaires.

Hypothesis: A regular HFN meditation practice over 6 weeks will further augment ECSS, and this will be correlated with an improvement in psychological outcomes such as psychological distress, sleep, mood and HRQoL.

Detailed description: Research Design

Design: We will conduct a single-arm uncontrolled pilot study with 40 patients. Patients aged 18-80 years diagnosed with CVS based on Rome criteria will be eligible to participate.

Exclusion criteria: 1. Major psychiatric illness such as schizophrenia, bipolar disease, and major depression or anxiety that is not controlled with medication or requiring inpatient care within the past year 2. History of suicidal attempt/ideation in the past year 3. Cognitive impairment that precludes the ability to meditate 4. Inability to sit for at least 30 minutes 5. Severe cardiopulmonary diseases, malignancy, or renal failure on dialysis 6. Other organic gastrointestinal diseases or systemic diseases including but not limited to inflammatory bowel disease and chronic liver diseases 7. Pregnancy at the time of enrollment 8. BMI \< 18 or \>35 9. Regular cannabis use (defined as daily or near-daily cannabis use) and 10. Individuals with significant prior meditation experience (continuous meditation practice for ≥ 3 months within a year prior to the study).

Patients will come for 2 study visits. Subjects will complete guided meditation sessions 3 x a week for six weeks delivered in the app via video, as well as pre- and post-meditation psychological state assessments. The app will automatically document meditation compliance, and study staff will be able to remind patients if compliance is inadequate. The app will be HIPAA compliant and only study staff will have access to PHI.

Study procedures:

Screening of potential study participants via web form and telephone. Study visit 1: Enrollment and baseline visit: Consenting, web app orientation, completion of baseline questionnaires, completion of first 30 min. meditation session using the app, with pre- and post-meditation blood draw.

Intervention: Six weeks of self-administered heart-focused meditation, consisting of 3 meditation sessions per week, each approximately 30 minutes in length, delivered via video guidance in the app.

Study visit 2: End-of-study visit. Completion of end-of-study questionnaires via the web app, final 30-min meditation session during the visit with pre-post session blood draw.

The web-based app: This will be custom-designed research (Heartsapp), which can be used on any smartphone or electronic tablet. The existing Heartsapp created by the HFN Institute will be modified and will be compliant with HIPAA privacy rules. Dr. Olafur Palsson at the University of North Carolina at Chapel Hill will serve as a consultant who has pioneered such applications. The HFN Institute has committed to modifying their existing app for research.

Psychological outcomes These will be measured using validated tools including the a. State-Trait-Anxiety Inventory (STAI)31 and profile of Mood States (POMS) c. Basic Symptom Inventory (BSI)33 at baseline, 3 and 6 weeks. Other parameters such as HRQOL (PROMIS), sleep quality (Pittsburgh Sleep Quality Index)35 and other measures of coping (COPE) will also be measured at these time points. Perceived intervention effectiveness will be assessed with a visual analog scale (VAS) ("0" not effective at all; "10" most effective imaginable) after intervention sessions at baseline and at end of study at 6 weeks.

Individual meditation protocol Subjects will be instructed to be seated in a comfortable position in a neutral room. They are instructed not to lie down during the session as this may promote sleep. The HFN meditation will last 30 minutes. There will be a prescribed progressive relaxation technique which will last for \~ 5-10 minutes followed by the heart-based meditation. This period of relaxation prepares them for the focused meditation. During the focused meditation, subjects will be instructed to bring their focus to the heart. They will be asked to make a gentle supposition that there is a source of light in the heart. They will be given specific instructions on how to deal with their thoughts. Unlike other forms of meditation, HFN meditation does not focus on the breath. Subjects are simply instructed to breathe normally during the session. The remainder of the meditation session (20 minutes) will be in silence. After the meditation session, the instructor will indicate that the session is ending. Participants will be asked to gently open their eyes, observe their inner state, and write down their observations.

Statistical analysis We expect that circulating endocannabinoids will increase immediately following HFN meditation and that this will be correlated with a reduction in state anxiety and improvement in mood. We will use a paired t-test to compare the circulating endocannabinoids at baseline (20 minutes prior) and 5-10 minutes post-intervention and compare patients' baseline and post-intervention psychological outcomes (STAI score for anxiety and POMS score for mood states) All of the baseline outcomes will also be compared with their values after the 6-week meditation checking further effects of the intervention. Transformation of the outcomes may be needed if the normality assumption is violated.

Blood collection procedures A small intravenous catheter will be placed in the forearm or wrist area and blood samples will be obtained (20 minutes prior) and 5-10 minutes post-intervention in the seated position. During each collection,10ml of blood will be collected in one red top serum-separating tube and will be refrigerated immediately. Plasma will be separated from blood by centrifugation and stored at -80 °C until analysis.

Endocannabinoid concentrations and related lipids Deuterated 2-AG and AEA will be added to the sera, followed by lipid extraction using solid phase columns as previously detailed.25 Concentrations of AEA, 2-AG, PEA, and OEA will be quantified by isotope dilution following measurement using atmospheric pressure, chemical ionization liquid chromatography/mass spectrometry (LC-APCI-MS) as described previously.14

Eligibility criteria: Inclusion Criteria:

* Patients aged 18 - 80 years of age
* Diagnosed with CVS based on Rome criteria

Exclusion Criteria:

* Major psychiatric illness such as schizophrenia, bipolar disease, and major depression or anxiety that is not controlled with medication or requiring inpatient care within the past year
* History of suicidal attempt/ideation in the past year
* Cognitive impairment that precludes the ability to meditate
* Inability to sit for at least 30 minutes
* Severe cardiopulmonary diseases, malignancy, or renal failure on dialysis
* Other organic gastrointestinal diseases or systemic diseases including but not limited to inflammatory bowel disease and chronic liver diseases
* Pregnancy at the time of enrollment
* BMI \< 18 or \>35
* Regular cannabis use (defined as daily or near-daily cannabis use) and
* Individuals with significant prior meditation experience (continuous meditation practice for ≥ 3 months within a year prior to the study).

Primary outcomes:
measure: State-Trait-Anxiety Inventory (STAI) (18) and Profile of Mood States (POMS)
timeFrame: 6 weeks
Secondary outcomes:
measure: Brief Symptom Inventory (BSI) - General Severity Index (GSI), Health-related Quality of Life (PROMIS), Sleep Quality (Pittsburgh Sleep Quality Index) Coping (COPE), and Visual Analog Scale (VAS) Effectiveness Score
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
Study officials:
References: