Healthy Subjects Clinical Trial
Official title:
Application of Diaphragmatic Breathing in Patients With Disorders of Gut-brain Interaction: Impact on Gastrointestinal and Psychological Symptoms as Well as Autonomic Nervous System
Patients with disorders of gut-brain interaction (DGBI) often present gastrointestinal symptoms that do not show noticeable irregularities in standard examinations. However, due to unclear causes and a high prevalence rate, this condition often exerts a profound impact on the physical and mental health of patients. The scope of DGBI encompasses conditions such as laryngopharyngeal reflux, functional dyspepsia, and irritable bowel syndrome. Previous research has confirmed that in patients with DGBI, their autonomic nervous system exhibits an imbalance, charact erized by decreased parasympathetic activity and dominant sympathetic activity. Diaphragmatic breathing helps reduce the respiratory rate and can stimulate parasympathetic activity while suppressing sympathetic activity. Hence, it is now officially recommended as an effective adjunct therapy for relieving symptoms of gastroesophageal reflux. Accordingly, this study plans to implement a randomized controlled trial, introducing diaphragmatic breathing to patients with DGBI who exhibit normal results in objective examinations. This work allows evaluate changes in their psychophysical symptoms before and after treatment, as well as alterations in the autonomic nervous system .
Status | Recruiting |
Enrollment | 600 |
Est. completion date | December 31, 2024 |
Est. primary completion date | December 31, 2024 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 70 Years |
Eligibility | Inclusion Criteria: Inclusion criteria for healthy subjects: 1. Age between 18 and 70, mentally alert and willing to sign the consent form for the study. 2. No gastrointestinal symptoms or use of gastrointestinal medication. Inclusion criteria for Laryngopharyngeal reflux disease subjects: 1. Age between 18 and 70, mentally alert and willing to sign the consent form for the study. 2. Gastroesophageal reflux disease (GERD) is defined as the condition characterized by experiencing symptoms for at least three months (such as hoarseness, sensation of a foreign body in the throat, chronic cough, and frequent throat clearing) occurring at least once a week. Reflux Symptom Index (RSI) is a standardized questionnaire for evaluating laryngopharyngeal reflux. It consists of nine reflux-related symptoms, with severity scores ranging from 0 (no symptoms) to 5 (most severe). A total score exceeding 13 indicates the criteria for inclusion of a patient as having laryngopharyngeal reflux. dyspepsia subjects: 1. Age between 18 and 70, mentally alert and willing to sign the consent form for the study. 2. Those who meet the definition of functional dyspepsia (FD). (Functional dyspepsia is chronic ( once a week , lasting for at least three months, at least six months before the first symptom) upper gastrointestinal symptoms (any of the following ) : postprandial abdominal distension, easy feeling of fullness, upper abdominal pain Or upper abdominal burning sensation, and no symptoms of gastrointestinal bleeding or significant weight loss, no abnormality after upper gastrointestinal endoscopy). Inclusion criteria for subjects with irritable bowel disorder: 1. Age between 18 and 70, mentally alert and willing to sign the consent form for the study. 2. meet the definition of irritable bowel disorder (IBS) . Irritable bowel syndrome is chronic ( once a week , lasting for at least three months) lower gastrointestinal symptoms: abdominal pain combined with diarrhea or constipation , and no symptoms of gastrointestinal bleeding or significant weight loss, no abnormalities after colonoscopy) . Exclusion Criteria: 1. Pregnant or lactating women. 2. Infected with antibiotic resistance. 3. Received endotracheal intubation in the past two months . 4. Having myocardial ischemia or recently experienced a myocardial infarction. 5. Unable to collaborate. |
Country | Name | City | State |
---|---|---|---|
Taiwan | Hualien Tzu Chi Hospital | Hualien City |
Lead Sponsor | Collaborator |
---|---|
Buddhist Tzu Chi General Hospital |
Taiwan,
Agusti A, Garcia-Pardo MP, Lopez-Almela I, Campillo I, Maes M, Romani-Perez M, Sanz Y. Interplay Between the Gut-Brain Axis, Obesity and Cognitive Function. Front Neurosci. 2018 Mar 16;12:155. doi: 10.3389/fnins.2018.00155. eCollection 2018. — View Citation
Ali MK, Chen JDZ. Roles of Heart Rate Variability in Assessing Autonomic Nervous System in Functional Gastrointestinal Disorders: A Systematic Review. Diagnostics (Basel). 2023 Jan 12;13(2):293. doi: 10.3390/diagnostics13020293. — View Citation
Ali MK, Liu L, Chen JH, Huizinga JD. Optimizing Autonomic Function Analysis via Heart Rate Variability Associated With Motor Activity of the Human Colon. Front Physiol. 2021 Jun 29;12:619722. doi: 10.3389/fphys.2021.619722. eCollection 2021. — View Citation
Ali MK, Saha S, Milkova N, Liu L, Sharma K, Huizinga JD, Chen JH. Modulation of the autonomic nervous system by one session of spinal low-level laser therapy in patients with chronic colonic motility dysfunction. Front Neurosci. 2022 Sep 1;16:882602. doi: — View Citation
Ambrosino N, Paggiaro PL, Macchi M, Filieri M, Toma G, Lombardi FA, Del Cesta F, Parlanti A, Loi AM, Baschieri L. A study of short-term effect of rehabilitative therapy in chronic obstructive pulmonary disease. Respiration. 1981;41(1):40-4. doi: 10.1159/0 — View Citation
Belafsky PC, Postma GN, Koufman JA. Validity and reliability of the reflux symptom index (RSI). J Voice. 2002 Jun;16(2):274-7. doi: 10.1016/s0892-1997(02)00097-8. — View Citation
Bernardi L, Gabutti A, Porta C, Spicuzza L. Slow breathing reduces chemoreflex response to hypoxia and hypercapnia, and increases baroreflex sensitivity. J Hypertens. 2001 Dec;19(12):2221-9. doi: 10.1097/00004872-200112000-00016. — View Citation
Bigger JT Jr, Albrecht P, Steinman RC, Rolnitzky LM, Fleiss JL, Cohen RJ. Comparison of time- and frequency domain-based measures of cardiac parasympathetic activity in Holter recordings after myocardial infarction. Am J Cardiol. 1989 Sep 1;64(8):536-8. d — View Citation
Browning KN, Travagli RA. Central control of gastrointestinal motility. Curr Opin Endocrinol Diabetes Obes. 2019 Feb;26(1):11-16. doi: 10.1097/MED.0000000000000449. — View Citation
Browning KN, Travagli RA. Central nervous system control of gastrointestinal motility and secretion and modulation of gastrointestinal functions. Compr Physiol. 2014 Oct;4(4):1339-68. doi: 10.1002/cphy.c130055. — View Citation
Callaghan B, Furness JB, Pustovit RV. Neural pathways for colorectal control, relevance to spinal cord injury and treatment: a narrative review. Spinal Cord. 2018 Mar;56(3):199-205. doi: 10.1038/s41393-017-0026-2. Epub 2017 Nov 16. — View Citation
Carabotti M, Scirocco A, Maselli MA, Severi C. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol. 2015 Apr-Jun;28(2):203-209. — View Citation
Chen J. Neuromodulation and Neurostimulation for the Treatment of Functional Gastrointestinal Disorders. Gastroenterol Hepatol (N Y). 2022 Jan;18(1):47-49. No abstract available. — View Citation
Ciccone AB, Siedlik JA, Wecht JM, Deckert JA, Nguyen ND, Weir JP. Reminder: RMSSD and SD1 are identical heart rate variability metrics. Muscle Nerve. 2017 Oct;56(4):674-678. doi: 10.1002/mus.25573. Epub 2017 Apr 8. — View Citation
DeGiorgio CM, Miller P, Meymandi S, Chin A, Epps J, Gordon S, Gornbein J, Harper RM. RMSSD, a measure of vagus-mediated heart rate variability, is associated with risk factors for SUDEP: the SUDEP-7 Inventory. Epilepsy Behav. 2010 Sep;19(1):78-81. doi: 10 — View Citation
Drossman DA, Hasler WL. Rome IV-Functional GI Disorders: Disorders of Gut-Brain Interaction. Gastroenterology. 2016 May;150(6):1257-61. doi: 10.1053/j.gastro.2016.03.035. No abstract available. — View Citation
Drossman DA, Tack J, Ford AC, Szigethy E, Tornblom H, Van Oudenhove L. Neuromodulators for Functional Gastrointestinal Disorders (Disorders of Gut-Brain Interaction): A Rome Foundation Working Team Report. Gastroenterology. 2018 Mar;154(4):1140-1171.e1. d — View Citation
Drossman DA. Functional Gastrointestinal Disorders: History, Pathophysiology, Clinical Features and Rome IV. Gastroenterology. 2016 Feb 19:S0016-5085(16)00223-7. doi: 10.1053/j.gastro.2016.02.032. Online ahead of print. — View Citation
Duan H, Cai X, Luan Y, Yang S, Yang J, Dong H, Zeng H, Shao L. Regulation of the Autonomic Nervous System on Intestine. Front Physiol. 2021 Jul 14;12:700129. doi: 10.3389/fphys.2021.700129. eCollection 2021. — View Citation
Halland M, Bharucha AE, Crowell MD, Ravi K, Katzka DA. Effects of Diaphragmatic Breathing on the Pathophysiology and Treatment of Upright Gastroesophageal Reflux: A Randomized Controlled Trial. Am J Gastroenterol. 2021 Jan 1;116(1):86-94. doi: 10.14309/aj — View Citation
Huang WJ, Shu CH, Chou KT, Wang YF, Hsu YB, Ho CY, Lan MY. Evaluating the autonomic nervous system in patients with laryngopharyngeal reflux. Otolaryngol Head Neck Surg. 2013 Jun;148(6):997-1002. doi: 10.1177/0194599813482103. Epub 2013 Mar 21. — View Citation
Jones R, Junghard O, Dent J, Vakil N, Halling K, Wernersson B, Lind T. Development of the GerdQ, a tool for the diagnosis and management of gastro-oesophageal reflux disease in primary care. Aliment Pharmacol Ther. 2009 Nov 15;30(10):1030-8. doi: 10.1111/ — View Citation
Julian LJ. Measures of anxiety: State-Trait Anxiety Inventory (STAI), Beck Anxiety Inventory (BAI), and Hospital Anxiety and Depression Scale-Anxiety (HADS-A). Arthritis Care Res (Hoboken). 2011 Nov;63 Suppl 11(0 11):S467-72. doi: 10.1002/acr.20561. No ab — View Citation
Karemaker JM. Counterpoint: respiratory sinus arrhythmia is due to the baroreflex mechanism. J Appl Physiol (1985). 2009 May;106(5):1742-3; discussion 1744. doi: 10.1152/japplphysiol.91107.2008a. No abstract available. — View Citation
Kocjan J, Adamek M, Gzik-Zroska B, Czyzewski D, Rydel M. Network of breathing. Multifunctional role of the diaphragm: a review. Adv Respir Med. 2017;85(4):224-232. doi: 10.5603/ARM.2017.0037. — View Citation
Labus JS, Bolus R, Chang L, Wiklund I, Naesdal J, Mayer EA, Naliboff BD. The Visceral Sensitivity Index: development and validation of a gastrointestinal symptom-specific anxiety scale. Aliment Pharmacol Ther. 2004 Jul 1;20(1):89-97. doi: 10.1111/j.1365-2 — View Citation
Lee Y, Yang MJ, Lai TJ, Chiu NM, Chau TT. Development of the Taiwanese Depression Questionnaire. Chang Gung Med J. 2000 Nov;23(11):688-94. — View Citation
Margolis KG, Cryan JF, Mayer EA. The Microbiota-Gut-Brain Axis: From Motility to Mood. Gastroenterology. 2021 Apr;160(5):1486-1501. doi: 10.1053/j.gastro.2020.10.066. Epub 2021 Jan 22. — View Citation
Montano N, Cogliati C, Porta A, Pagani M, Malliani A, Narkiewicz K, Abboud FM, Birkett C, Somers VK. Central vagotonic effects of atropine modulate spectral oscillations of sympathetic nerve activity. Circulation. 1998 Oct 6;98(14):1394-9. doi: 10.1161/01 — View Citation
Naliboff BD, Benton D, Solomon GF, Morley JE, Fahey JL, Bloom ET, Makinodan T, Gilmore SL. Immunological changes in young and old adults during brief laboratory stress. Psychosom Med. 1991 Mar-Apr;53(2):121-32. doi: 10.1097/00006842-199103000-00002. — View Citation
Otzenberger H, Gronfier C, Simon C, Charloux A, Ehrhart J, Piquard F, Brandenberger G. Dynamic heart rate variability: a tool for exploring sympathovagal balance continuously during sleep in men. Am J Physiol. 1998 Sep;275(3):H946-50. doi: 10.1152/ajphear — View Citation
Ouyang H, Yin J, Wang Z, Pasricha PJ, Chen JD. Electroacupuncture accelerates gastric emptying in association with changes in vagal activity. Am J Physiol Gastrointest Liver Physiol. 2002 Feb;282(2):G390-6. doi: 10.1152/ajpgi.00272.2001. — View Citation
Phillips RJ, Powley TL. Innervation of the gastrointestinal tract: patterns of aging. Auton Neurosci. 2007 Oct 30;136(1-2):1-19. doi: 10.1016/j.autneu.2007.04.005. Epub 2007 May 29. — View Citation
Rao M, Gershon MD. The bowel and beyond: the enteric nervous system in neurological disorders. Nat Rev Gastroenterol Hepatol. 2016 Sep;13(9):517-28. doi: 10.1038/nrgastro.2016.107. Epub 2016 Jul 20. — View Citation
Revicki DA, Wood M, Wiklund I, Crawley J. Reliability and validity of the Gastrointestinal Symptom Rating Scale in patients with gastroesophageal reflux disease. Qual Life Res. 1998 Jan;7(1):75-83. doi: 10.1023/a:1008841022998. — View Citation
Shaffer F, Ginsberg JP. An Overview of Heart Rate Variability Metrics and Norms. Front Public Health. 2017 Sep 28;5:258. doi: 10.3389/fpubh.2017.00258. eCollection 2017. — View Citation
Shaffer F, McCraty R, Zerr CL. A healthy heart is not a metronome: an integrative review of the heart's anatomy and heart rate variability. Front Psychol. 2014 Sep 30;5:1040. doi: 10.3389/fpsyg.2014.01040. eCollection 2014. — View Citation
Stauss HM. Heart rate variability. Am J Physiol Regul Integr Comp Physiol. 2003 Nov;285(5):R927-31. doi: 10.1152/ajpregu.00452.2003. No abstract available. — View Citation
Taft TH, Triggs JR, Carlson DA, Guadagnoli L, Tomasino KN, Keefer L, Pandolfino JE. Validation of the oesophageal hypervigilance and anxiety scale for chronic oesophageal disease. Aliment Pharmacol Ther. 2018 May;47(9):1270-1277. doi: 10.1111/apt.14605. E — View Citation
Taylor JM. Psychometric analysis of the Ten-Item Perceived Stress Scale. Psychol Assess. 2015 Mar;27(1):90-101. doi: 10.1037/a0038100. Epub 2014 Oct 27. — View Citation
Umetani K, Singer DH, McCraty R, Atkinson M. Twenty-four hour time domain heart rate variability and heart rate: relations to age and gender over nine decades. J Am Coll Cardiol. 1998 Mar 1;31(3):593-601. doi: 10.1016/s0735-1097(97)00554-8. — View Citation
Wong MW, Hsiao SH, Wang JH, Yi CH, Liu TT, Lei WY, Hung JS, Liang SW, Lin L, Gyawali CP, Chen PR, Chen CL. Esophageal Hypervigilance and Visceral Anxiety Contribute to Symptom Severity of Laryngopharyngeal Reflux. Am J Gastroenterol. 2023 May 1;118(5):786 — View Citation
Yadlapati R, Gyawali CP, Pandolfino JE; CGIT GERD Consensus Conference Participants. AGA Clinical Practice Update on the Personalized Approach to the Evaluation and Management of GERD: Expert Review. Clin Gastroenterol Hepatol. 2022 May;20(5):984-994.e1. — View Citation
Yu Y, Wei R, Liu Z, Xu J, Xu C, Chen JDZ. Ameliorating Effects of Transcutaneous Electrical Acustimulation Combined With Deep Breathing Training on Refractory Gastroesophageal Reflux Disease Mediated via the Autonomic Pathway. Neuromodulation. 2019 Aug;22 — View Citation
Yuan Y, Ali MK, Mathewson KJ, Sharma K, Faiyaz M, Tan W, Parsons SP, Zhang KK, Milkova N, Liu L, Ratcliffe E, Armstrong D, Schmidt LA, Chen JH, Huizinga JD. Associations Between Colonic Motor Patterns and Autonomic Nervous System Activity Assessed by High — View Citation
* Note: There are 45 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Change from Baseline on the Functional Dyspepsia Scale(FD) at 14 days | Possible scores range from 0 (Very slightly) to 6 (Very serious) 0=Very slightly 1=Slight 2=A little slightly 3=About medium 4=A bit serious 5=Severe 6=Very serious Change = (day 28 Score - Baseline Score). | Baseline and day 28 | |
Primary | Change from Baseline on the Irritable Bowel Syndrome Scale(IBS) at 14 days | Possible scores range from 1 (Never) to 5 (Always)
1=Never 2=Sometimes 3=Often4=most of the time 5=Always Change = (day 28 Score - Baseline Score). |
Baseline and day 28 | |
Primary | Change from Baseline on the Gastroesophageal Reflux Disease Questionnaire(GERDQ) at 14 days | Possible scores range from 1 (Never) to 3 (4~7days) 0=Never 1=1 day 2=2~3days 3=4~7days Change = (day 28 Score - Baseline Score). | Baseline and day 28 | |
Primary | Change from Baseline on the Reflux Symptom Index (RSI) at 14 days | Possible scores range from 0 (no symptoms) to 5 (most severe) 0= No Problem 1=very slight 2=slight 3=About medium 4=moderate to severe 5=Severe Problem Change = (day 28 Score - Baseline Score). | Baseline and day 28 | |
Primary | Change from Baseline in Pain on the Gastrointestinal symptom rating scale (GSRS) at 14 days | Possible scores range from 1 (No pain) to 4 (Worst possible pain)
1=No pain 2=Mild 3=Moderate 4=Worst possible pain Change = (day 28 Score - Baseline Score). |
Baseline and day 28 | |
Primary | Change from Baseline on the Pittsburgh sleep quality index (PSQI) at 14 days | Possible scores range from 0 (Never) to 3 (Occurs three times a week times or more) 0=Never 1=Less than once a week 2=Occurs once or twice a week 3=Occurs three times a week times or more Change = (day 28 Score - Baseline Score). | Baseline and day 28 | |
Primary | Change from Baseline on the Taiwanese Depression Scale (TDQ) at 14 days | Possible scores range from 0 (Never) to 3 (Always) 0=Never 1=Sometimes 2=Often 3=Always Change = (day 28 Score - Baseline Score). | Baseline and day 28 | |
Primary | Change from Baseline on the State-Trait Anxiety Inventory (STAI) at 14 days | Possible scores range from 1 (Never) to 4 (Always)
1=Never 2=Sometimes 3=Often 4=Always Change = (day 28 Score - Baseline Score). |
Baseline and day 28 | |
Primary | Change from Baseline on the Perceived Stress Scale(PSS-10) at 14 days | Possible scores range from 0 (Never) to 4 (Always) 0=Never 1=Rarely 2=Sometimes 3=Often 4=Always Change = (day 28 Score - Baseline Score). | Baseline and day 28 | |
Primary | Change from Baseline on the Esophageal Hypervigilance and Anxiety Scale (EHAS) at 14 days | Possible scores range from 0 (Strongly disagree) to 4 (Strongly agree) 0=Strongly disagree 1=Somewhat disagree 2=Neiteher agree nor disagree 3=Somewhat agree 4 =Strongly agree Change = (day 28 Score - Baseline Score). | Baseline and day 28 | |
Primary | Change from Baseline on the Laryngeal Hypervigilance and Anxiety Scale (LHAS) at 14 days | Possible scores range from 0 (Strongly disagree) to 4 (Strongly agree) 0=Strongly disagree 1=Somewhat disagree 2=Neiteher agree nor disagree 3=Somewhat agree 4 =Strongly agree Change = (day 28 Score - Baseline Score). | Baseline and day 28 | |
Primary | Change from Baseline on the Visceral Sensitivity Index (VSI) at 14 days | Possible scores range from 1 (Strongly disagree) to 6 (Strongly agree)
1=Strongly agree 2=Moderately agree 3=Mildly agree 4=Mildly disagree 5 =Moderately disagree 6=Strongly disagree Change = (day 28 Score - Baseline Score). |
Baseline and day 28 |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT05483998 -
A Study to Evaluate Single and Multiple Doses of TLC-2716 in Healthy Participants
|
Phase 1 | |
Recruiting |
NCT02235012 -
Cognitive Biases Under Ketamine
|
N/A | |
Recruiting |
NCT02417714 -
Prospective Evaluation of Next Generation CT Reconstruction (NextGenIR)
|
||
Completed |
NCT05088343 -
Effect of Hetrombopag on the Pharmacokinetics of Rosuvastatin in Healthy Subjects
|
Phase 1 | |
Completed |
NCT04418973 -
Analysis of Breath Volatile Organic Compounds After Dyspnea Induced in the Healthy Subject.
|
N/A | |
Not yet recruiting |
NCT06248801 -
Vildagliptin and Metformin Tablets 50/1000 mg Relative to GALVUS MET (50mg/1000 mg) Tablets
|
Phase 1 | |
Terminated |
NCT04068259 -
Single Ascending Dose Study of PBI-4547 in Healthy Subjects
|
Phase 1 | |
Completed |
NCT03279302 -
Trial to Evaluate the PK Profile of Glepaglutide (ZP1848) After a Single IV and After Multiple SC Injections in Healthy Subjects
|
Phase 1 | |
Not yet recruiting |
NCT06233162 -
Febuxostat 80 mg Tablets Relative to Feburic® 80 mg Tablets
|
Phase 1 | |
Recruiting |
NCT04159844 -
Evaluation of the Stiffness and Pressure Applied on the Lower Leg by a New Compression Bandage on Healthy Subjects
|
N/A | |
Completed |
NCT06137911 -
Evaluation of Safety, Tolerability & Pharmacokinetics of JYP0061 in Healthy Adults.
|
Phase 1 | |
Completed |
NCT04849286 -
Measurement of HTL0016878 in Cerebrospinal Fluid
|
Phase 1 | |
Not yet recruiting |
NCT06233227 -
Dutasteride Soft Capsule 0.5 mg Relative to Avodart 0.5 mg Soft Capsule
|
Phase 1 | |
Completed |
NCT04096157 -
A Study to Assess Isavuconazole Following a Single Dose of Isavuconazonium Sulfate Intravenous Solution Via Nasogastric (NG) Tube Compared to a Single Dose of Oral Capsules Under Fasting Conditions in Healthy Participants
|
Phase 1 | |
Completed |
NCT01200368 -
Trial Evaluating a 13-valent Pneumococcal Conjugate Vaccine Given With Diphtheria, Tetanus, and Acellular Pertussis Vaccine (DTaP) in Healthy Japanese Infants
|
Phase 3 | |
Recruiting |
NCT05805033 -
Peri-Implant Soft Tissue Integration in Humans: Influence of Material
|
N/A | |
Completed |
NCT04027803 -
Comparative Study of Pharmacokinetics, Pharmacodynamics, Safety, and Immunogenicity of Single Intravenous Doses of BCD-148 and Soliris®
|
Phase 1 | |
Recruiting |
NCT03467880 -
Multicenter Study of Impulse Oscillometry in Chinese
|
N/A | |
Completed |
NCT02903095 -
Single Ascending Dose Study of TD-1439 in Healthy Subjects
|
Phase 1 | |
Active, not recruiting |
NCT02341508 -
A Phase 1a, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Evaluate Lpathomab in Healthy Volunteers
|
Phase 1 |