Autoimmune Gastrointestinal Dysmotility: Symptoms, Pathogenesis and Treatment

March 9, 2023 updated by: Johns Hopkins University
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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Actual)

1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21224
        • Johns Hopkins Bayview Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

15 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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.

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Patients with autoimmune dysmotility receiving IVIG infusions
Other: Current Intravenous Immunoglobulin (IVIG) treatment
Questionnaires every two months for patients with a diagnosis of autoimmune dysmotility that are receiving Intravenous Immunoglobulin (IVIG) treatment.
Patients with autoimmune dysmotility without IVIG infusions
Other: No Intravenous Immunoglobulin (IVIG) treatment
Questionnaires every two months for patients with a diagnosis of autoimmune dismotility that are not receiving Intravenous Immunoglobulin (IVIG) treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in upper gastrointestinal symptom severity as assessed by the Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index
Time Frame: Every two months up to 2 years.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Quality of Life as assessed by the Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life scale
Time Frame: Every two months up to 2 years.
The effect of Autoimmune Dysmotility symptoms on quality of life assessed by the Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life (PAGI-QoL). The PAGI-QOL instrument consists of 30 items, each with response options based on a 6-point scale and with a recall period of the previous 2 weeks. The items are grouped into 5 dimensions: Daily Activities, Clothing, Diet and Food Habits, Relationship and Psychological Well-being and Distress. A score per dimension as well as a total score can be calculated. The PAGI-QOL scores range from 0 (lowest QoL) to 5 (highest QoL).
Every two months up to 2 years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Johns Hopkins University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 22, 2021

Primary Completion (Actual)

September 29, 2022

Study Completion (Actual)

September 29, 2022

Study Registration Dates

First Submitted

April 22, 2021

First Submitted That Met QC Criteria

April 22, 2021

First Posted (Actual)

April 26, 2021

Study Record Updates

Last Update Posted (Actual)

March 13, 2023

Last Update Submitted That Met QC Criteria

March 9, 2023

Last Verified

March 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00087869

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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