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

NCT04875949 | Completed

• 1 other identifier: DISAUT-AB ICH
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pure Autonomic Failure; Amyotrophic Lateral Sclerosis; Postural Orthostatic Tachycardia Syndrome; Anti-Cholinergic Receptors Antibodies

Keywords

Neural control of circulation and respiration; Anti-Cholinergic receptors antibodies; Power Spectrum Analysis

Outcome Measures

Primary Outcomes (4)

• Prevalence of plasma anti-AChR Abs in PAF, ALS and POTS

  Number of patients with plasma anti-AChR Abs

  3 years

• Effects of anti-AChR Abs removal on dysautonomic symptoms

  COMPASS31 scores (range 0-100; 0 best -100 worst)

  3 years

• Time course of dysautonomia symptoms

  COMPASS31 scores (range: 0-100; 0 best-100 worst)

  3 years

• Time course of orthostatic tolerance

  Orthostatic tolerance (minutes)

  3 years

Study Arms (1)

Anti-AChRs Abs positive patients

EXPERIMENTAL

Immunoabsorption

Procedure: Immunoabsorption/plasmapheresis procedure

Interventions

Immunoabsorption/plasmapheresis procedure PROCEDURE

Anti-AChRs Abs positive patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Istituto Clinico Humanitas: lead
• Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta: collaborator
• Fondazione Salvatore Maugeri: collaborator

Study Sites (1)

Humanitas Research Hospital

Rozzano, 20089, Italy

Location

Related Publications (14)

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  PMID: 10995864 BACKGROUND

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  PMID: 16221781 BACKGROUND

• Furlan R, Jacob G, Snell M, Robertson D, Porta A, Harris P, Mosqueda-Garcia R. Chronic orthostatic intolerance: a disorder with discordant cardiac and vascular sympathetic control. Circulation. 1998 Nov 17;98(20):2154-9. doi: 10.1161/01.cir.98.20.2154.

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  PMID: 18951069 BACKGROUND

• Sabatelli M, Eusebi F, Al-Chalabi A, Conte A, Madia F, Luigetti M, Mancuso I, Limatola C, Trettel F, Sobrero F, Di Angelantonio S, Grassi F, Di Castro A, Moriconi C, Fucile S, Lattante S, Marangi G, Murdolo M, Orteschi D, Del Grande A, Tonali P, Neri G, Zollino M. Rare missense variants of neuronal nicotinic acetylcholine receptor altering receptor function are associated with sporadic amyotrophic lateral sclerosis. Hum Mol Genet. 2009 Oct 15;18(20):3997-4006. doi: 10.1093/hmg/ddp339. Epub 2009 Jul 23.

  PMID: 19628475 BACKGROUND

• Vernino S, Adamski J, Kryzer TJ, Fealey RD, Lennon VA. Neuronal nicotinic ACh receptor antibody in subacute autonomic neuropathy and cancer-related syndromes. Neurology. 1998 Jun;50(6):1806-13. doi: 10.1212/wnl.50.6.1806.

  PMID: 9633732 BACKGROUND

• Furlan R, Piazza S, Bevilacqua M, Turiel M, Norbiato G, Lombardi F, Malliani A. Pure Autonomic Failure: complex abnormalities in the neural mechanisms regulating the cardiovascular system. J Auton Nerv Syst. 1995 Mar 2;51(3):223-35. doi: 10.1016/0165-1838(94)00135-7.

  PMID: 7769156 BACKGROUND

• Barbic F, Perego F, Canesi M, Gianni M, Biagiotti S, Costantino G, Pezzoli G, Porta A, Malliani A, Furlan R. Early abnormalities of vascular and cardiac autonomic control in Parkinson's disease without orthostatic hypotension. Hypertension. 2007 Jan;49(1):120-6. doi: 10.1161/01.HYP.0000250939.71343.7c. Epub 2006 Nov 13.

  PMID: 17101845 BACKGROUND

• Porta A, Castiglioni P, Di Rienzo M, Bari V, Bassani T, Marchi A, Takahashi AC, Tobaldini E, Montano N, Catai AM, Barbic F, Furlan R, Cividjian A, Quintin L. Short-term complexity indexes of heart period and systolic arterial pressure variabilities provide complementary information. J Appl Physiol (1985). 2012 Dec 15;113(12):1810-20. doi: 10.1152/japplphysiol.00755.2012. Epub 2012 Oct 25.

  PMID: 23104699 BACKGROUND

• Furlan R, Porta A, Costa F, Tank J, Baker L, Schiavi R, Robertson D, Malliani A, Mosqueda-Garcia R. Oscillatory patterns in sympathetic neural discharge and cardiovascular variables during orthostatic stimulus. Circulation. 2000 Feb 29;101(8):886-92. doi: 10.1161/01.cir.101.8.886.

  PMID: 10694528 BACKGROUND

• Barbic F, Galli M, Dalla Vecchia L, Canesi M, Cimolin V, Porta A, Bari V, Cerri G, Dipaola F, Bassani T, Cozzolino D, Pezzoli G, Furlan R. Effects of mechanical stimulation of the feet on gait and cardiovascular autonomic control in Parkinson's disease. J Appl Physiol (1985). 2014 Mar 1;116(5):495-503. doi: 10.1152/japplphysiol.01160.2013. Epub 2014 Jan 16.

  PMID: 24436294 BACKGROUND

• Low PA. Composite autonomic scoring scale for laboratory quantification of generalized autonomic failure. Mayo Clin Proc. 1993 Aug;68(8):748-52. doi: 10.1016/s0025-6196(12)60631-4.

  PMID: 8392653 BACKGROUND

• Chio A, Mora G, Restagno G, Brunetti M, Ossola I, Barberis M, Ferrucci L, Canosa A, Manera U, Moglia C, Fuda G, Traynor BJ, Calvo A. UNC13A influences survival in Italian amyotrophic lateral sclerosis patients: a population-based study. Neurobiol Aging. 2013 Jan;34(1):357.e1-5. doi: 10.1016/j.neurobiolaging.2012.07.016. Epub 2012 Aug 22.

  PMID: 22921269 BACKGROUND

• Chio A, Calvo A, Moglia C, Mazzini L, Mora G; PARALS study group. Phenotypic heterogeneity of amyotrophic lateral sclerosis: a population based study. J Neurol Neurosurg Psychiatry. 2011 Jul;82(7):740-6. doi: 10.1136/jnnp.2010.235952. Epub 2011 Mar 14.

  PMID: 21402743 BACKGROUND

MeSH Terms

Conditions

Pure Autonomic Failure; Amyotrophic Lateral Sclerosis; Postural Orthostatic Tachycardia Syndrome; Respiratory Aspiration

Condition Hierarchy (Ancestors)

Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Central Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Orthostatic Intolerance; Respiration Disorders; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Raffaello Furlan, Prof.

  Humanitas Research Hospital, Humanitas University

  PRINCIPAL INVESTIGATOR

• Franca Barbic, MD

  Humanitas Research Hospital, Humanitas University, Rozzano

  STUDY CHAIR

• Raffaello Furlan, Prof.

  Humanitas Research Hospital, Humanitas University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2021
• First Posted: May 6, 2021
• Study Start: April 1, 2016
• Primary Completion: January 1, 2019
• Study Completion: April 1, 2019
• Last Updated: May 6, 2021

Record last verified: 2021-05

Locations

IT (1)