Anti-Cholinergic Receptors Antibodies, Autonomic Profile and Dysautonomia Symptoms in PAF, ALS and POTS (DISAUT-AB) (DISAUT-AB)

May 3, 2021 updated by: Istituto Clinico Humanitas

Anti-Cholinergic Receptors Antibodies and Dysautonomia Symptoms Relationships in Pure Autonomic Failure, Amyotrophic Lateral Sclerosis, Postural Orthostatic Tachycardia Syndrome: a Pathophysiology Based Therapeutic New Strategy.

Anti alfa-3 and alfa-7 ganglionic cholinergic receptors (anti-AChRs) antibodies (Abs) plasma removal by plasmapheresis (1,2) acutely improved dysautonomia symptoms in case reports with Pure Autonomic Failure (PAF) (3). We shall assess the prevalence of anti-AChRs Ab and the relationship among Ab titer, cardiovascular autonomic profile and symptoms in neurodegenerative diseases characterized by similar dysautonomia symptoms such as PAF, Amyotrophic Lateral Sclerosis (ALS) and Postural Orthostatic Tachycardia Syndrome (POTS) (4). Ab positive patients will undergo selective immunoabsorption once a week up to achievement of Ab titer lower than 65% of baseline followed by immunosuppressive therapy with prednisone. Both Ab positive and negative groups will undergo anti-AChR Abs, autonomic profile and dysautonomia symptoms assessment, every 4 months up to 3 years. Evidence of correlation among reduced Ab titer and autonomic profile and symptoms improvement may result in new effective therapy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PAF is a rare neurodegenerative disorder characterized by symptoms due to sympathetic failure, such as orthostatic hypotension and syncope, and deficient parasympathetic activity such as constipation, urinary retention and decreased salivation (3). Plasma anti-AChRs Abs were found in PAF (1, 2, 5) and in POTS (6), raising the possibility that Ab mediated alterations in the ganglionic cholinergic function might induce autonomic abnormalities and related symptoms. Anti-AchRs Abs removal by plasmapheresis was associated with acute improvement of orthostatic tolerance in PAF single case report (2).

There is no data on the medium/long term clinical follow-up of these patients. Nothing is known about the time course of the relationships among Abs plasma titer, neural autonomic profile and symptoms if a selective immunoabsorption procedure is combined with drug immunosoppression (Prednisone) to lower Ab levels and potentially ameliorate ganglionic function.

Finally, it is unknown whether a neurodegenerative disease with concomitant dysautonomia symptoms such as the Amyotrophic Lateral Sclerosis (ALS) may share an analogous anti-AChRs Ab profile. Variations in cholinergic receptor subunits 3 and 4 were observed in ALS but no plasma anti-AChRs Abs were searched for (7). Abs removal by immunoabsorption technique combined with drug immunosoppression might represent a new effective therapy for dysautonomia symptoms in ALS as well as in POTS and PAF.

Hyphotesis and Significance:

  • Changes in anti-AChR Abs plasma titer may be mirrored by modifications in the cardiovascular autonomic profile, as assessed by spectrum analysis of RR and arterial pressure variability, and be related to fluctuations in the magnitude of dysautonomia symptoms in PAF, ALS and POTS patients.
  • Plasma anti-AChR Abs might underlie dysautonomia symptoms associated to neurodegenerative disorders such as ASL and POTS
  • Plasma anti-AChR Abs removal by selective immunoabsorption techniques may improve ganglionic transmission leading to clinical amelioration and represent a new effective etiologic therapy for these diseases.

Specific Aim:

Aim 1: To evaluate the prevalence of plasma anti-AChR Abs in patients affected by PAF, ALS and POTS .

Aim 2: To address the time course and relationships of anti-AChR Abs plasma titers, cardiovascular autonomic profile and dysautonomia symptoms before and after anti-AChR Abs plasma removal by selective immunoabsorption technique in PAF, ALS and POTS patients. The core laboratory of the Neuroimmunology Unit of Istituto Neurologico Besta will provide expertise and facilities for assessing plasma anti-AChR Abs. The clinical laboratory of Clinica Medica Syncope Unit (Humanitas) will provide the know-how and facilities for patients neural autonomic assessment.

Aim 3:To set up a new therapeutic strategy based on selective immunoabsorption technique sessions combined with drug immunosuppression (Prednisone) in patients with anti-AChR Abs.

Study Type

Interventional

Enrollment (Actual)

75

Phase

  • Not Applicable

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

  • Italy
      • Rozzano, Italy, 20089
        • Humanitas Research Hospital

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

• Patients, older than 18 years affected by PAF, ALS and POTS, with dysautonomia symptoms assessed by clinical evaluation and by the Composite Autonomic Scoring Scale (CASS)

Exclusion Criteria:

  • Hepatic, renal, heart and other secondary causes of autonomic dysfunction
  • History/familiarity with seizures
  • Atrial fibrillation and other relevant cardiac rhythm disturbances
  • Diabetes
  • Other neurological or psychiatric diseases
  • Pacemakers or other electronic implants inserted into the body
  • Coronary disorders, elevated intracranial blood pressure
  • Assumption of drugs facilitating seizures, psychiatric drugs, alcohol abuse

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

  • Primary Purpose: Supportive Care
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Anti-AChRs Abs positive patients
Immunoabsorption
Procedure: Immunoabsorption/plasmapheresis procedure

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prevalence of plasma anti-AChR Abs in PAF, ALS and POTS
Time Frame: 3 years
Number of patients with plasma anti-AChR Abs
3 years
Effects of anti-AChR Abs removal on dysautonomic symptoms
Time Frame: 3 years
COMPASS31 scores (range 0-100; 0 best -100 worst)
3 years
Time course of dysautonomia symptoms
Time Frame: 3 years
COMPASS31 scores (range: 0-100; 0 best-100 worst)
3 years
Time course of orthostatic tolerance
Time Frame: 3 years
Orthostatic tolerance (minutes)
3 years

Collaborators and Investigators

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

Sponsor

Istituto Clinico Humanitas

Collaborators

Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
Fondazione Salvatore Maugeri

Investigators

  • Principal Investigator: Raffaello Furlan, Prof., Humanitas Research Hospital, Humanitas University
  • Study Chair: Franca Barbic, MD, Humanitas Research Hospital, Humanitas University, Rozzano
  • Study Director: Raffaello Furlan, Prof., Humanitas Research Hospital, Humanitas University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

April 1, 2016

Primary Completion (Actual)

January 1, 2019

Study Completion (Actual)

April 1, 2019

Study Registration Dates

First Submitted

January 12, 2021

First Submitted That Met QC Criteria

May 3, 2021

First Posted (Actual)

May 6, 2021

Study Record Updates

Last Update Posted (Actual)

May 6, 2021

Last Update Submitted That Met QC Criteria

May 3, 2021

Last Verified

May 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DISAUT-AB ICH

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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