Autoimmune Gastrointestinal Dysmotility: Symptoms, Pathogenesis and Treatment

NCT04859829 | Terminated

• 1 other identifier: IRB00087869
• Study Type: observational
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Autoimmune gastrointestinal dysmotility syndromes are poorly understood, and often difficult to treat because the underlying pathogenesis is unclear. Refractory symptoms result in an impaired quality of life. The presence of positive serum autoantibodies to peripheral nervous system gangliosides and glycoproteins is suggestive of a possible mechanism. Immunomodulator treatments have shown benefit in case reports and case series but standardized data for treatment response is lacking. Therefore, our primary aims are to further characterize this syndrome in terms of symptoms, laboratory testing, pathology, and assess treatment response of immunomodulator therapy. Our research plan involves identifying this subset of patients with autoimmune gastrointestinal dysmotility and dysautonomia, and studying them as they are managed by their gastroenterologists.The study team will administer symptom-based questionnaires in a systematic manner to assess the clinical trajectory of this population and treatment response. The investigators will also analyze laboratory values (antibody titers, tilt testing, inflammatory markers) and study pathology specimens (enteric and skin biopsies) obtained from this cohort to gain a deeper understanding of the pathogenesis of their disease.

Conditions

Dysmotility Syndrome; Autoimmunity

Outcome Measures

Primary Outcomes (1)

• Change in upper gastrointestinal symptom severity as assessed by the Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index

  The Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM) is composed of 20 items and 6 sub-scales: heartburn/regurgitation (7 items), nausea/vomiting (3 items), postprandial fullness/early satiety (4 items), bloating (2 items), upper abdominal pain (2 items), and lower abdominal pain (2 items). Sub-scale scores are calculated by averaging across items comprising the sub-scale; scores vary from 0 (none or absent) to 5 (very severe).

  Every two months up to 2 years.

Secondary Outcomes (1)

• Change in Quality of Life as assessed by the Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life scale

  Every two months up to 2 years.

Study Arms (2)

Patients with autoimmune dysmotility receiving IVIG infusions

Other: Current Intravenous Immunoglobulin (IVIG) treatment

Patients with autoimmune dysmotility without IVIG infusions

Other: No Intravenous Immunoglobulin (IVIG) treatment

Interventions

Current Intravenous Immunoglobulin (IVIG) treatment OTHER

Questionnaires every two months for patients with a diagnosis of autoimmune dysmotility that are receiving Intravenous Immunoglobulin (IVIG) treatment.

Patients with autoimmune dysmotility receiving IVIG infusions

No Intravenous Immunoglobulin (IVIG) treatment OTHER

Questionnaires every two months for patients with a diagnosis of autoimmune dismotility that are not receiving Intravenous Immunoglobulin (IVIG) treatment.

Patients with autoimmune dysmotility without IVIG infusions

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with autoimmune autonomic ganglionopathy (AAG) or autoimmune autonomic neuropathy. Postural orthostatic tachycardia syndrome (POTS) and gastrointestinal (GI) dysmotility.

You may qualify if:

• Males and females, Aged\>15
• Evidence of enteric dysmotility with documented abnormality on objective testing which may include high resolution esophageal manometry, gastric emptying scintigraphy, SmartPill Wireless Motility Capsule, Sitz marker studies, antroduodenal manometry or anorectal manometry.
• English proficiency and literacy sufficient to sign consent form and fill out questionnaires.
• Previous Mayo paraneoplastic panel testing.
• Referring gastroenterologist has recommended intravenous immunoglobulin (IVIg) therapy.

You may not qualify if:

• Non-autoimmune causes of enteric dysmotility (diabetes, adrenal insufficiency, Parkinson's, thyroid, electrolytes, drugs, malignancy).
• Pregnancy as documented in EPIC with serum or urine Human chorionic gonadotropin (hCG) testing
• If participants believe that they are pregnant, they will need to notify a study physician who will order a serum or urine hCG test for pregnancy within EPIC and remove them from the study if the test results come back positive.
• Previous treatment with IVIg.

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (1)

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 21224, United States

Location

Related Publications (1)

• Pasricha PJ, McKnight M, Villatoro L, Barahona G, Brinker J, Hui K, Polydefkis M, Burns R, McMahan ZH, Gould N, Goodman B, Hentz J, Treisman G. Joint Hypermobility, Autonomic Dysfunction, Gastrointestinal Dysfunction, and Autoimmune Markers: Clinical Associations and Response to Intravenous Immunoglobulin Therapy. Am J Gastroenterol. 2024 Nov 1;119(11):2298-2306. doi: 10.14309/ajg.0000000000002910. Epub 2024 Jun 24.

  PMID: 38912927 DERIVED

MeSH Terms

Conditions

Ciliary Motility Disorders; Autoimmune Diseases

Interventions

Immunoglobulins, Intravenous; Therapeutics

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Ciliopathies; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Pankaj J Pasricha, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2021
• First Posted: April 26, 2021
• Study Start: April 22, 2021
• Primary Completion: September 29, 2022
• Study Completion: September 29, 2022
• Last Updated: March 13, 2023

Record last verified: 2022-03

Locations

US (1)