Amyotrophic Lateral Sclerosis Clinical Trial
— DISAUT-ABOfficial title:
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.
NCT number | NCT04875949 |
Other study ID # | DISAUT-AB ICH |
Secondary ID | |
Status | Completed |
Phase | N/A |
First received | |
Last updated | |
Start date | April 2016 |
Est. completion date | April 2019 |
Verified date | May 2021 |
Source | Istituto Clinico Humanitas |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 75 |
Est. completion date | April 2019 |
Est. primary completion date | January 2019 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
Italy | Humanitas Research Hospital | Rozzano |
Lead Sponsor | Collaborator |
---|---|
Istituto Clinico Humanitas | Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta, Fondazione Salvatore Maugeri |
Italy,
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. — View Citation
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. Epub 2006 Nov 13. — View Citation
Chiò 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. — View Citation
Chiò 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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
Low PA. Composite autonomic scoring scale for laboratory quantification of generalized autonomic failure. Mayo Clin Proc. 1993 Aug;68(8):748-52. — View Citation
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. — View Citation
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. — View Citation
Schroeder C, Vernino S, Birkenfeld AL, Tank J, Heusser K, Lipp A, Benter T, Lindschau C, Kettritz R, Luft FC, Jordan J. Plasma exchange for primary autoimmune autonomic failure. N Engl J Med. 2005 Oct 13;353(15):1585-90. — View Citation
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. — View Citation
Vernino S, Hopkins S, Wang Z. Autonomic ganglia, acetylcholine receptor antibodies, and autoimmune ganglionopathy. Auton Neurosci. 2009 Mar 12;146(1-2):3-7. doi: 10.1016/j.autneu.2008.09.005. Epub 2008 Oct 31. Review. — View Citation
Vernino S, Low PA, Fealey RD, Stewart JD, Farrugia G, Lennon VA. Autoantibodies to ganglionic acetylcholine receptors in autoimmune autonomic neuropathies. N Engl J Med. 2000 Sep 21;343(12):847-55. — View Citation
* Note: There are 14 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Prevalence of plasma anti-AChR Abs in PAF, ALS and POTS | Number of patients with plasma anti-AChR Abs | 3 years | |
Primary | Effects of anti-AChR Abs removal on dysautonomic symptoms | COMPASS31 scores (range 0-100; 0 best -100 worst) | 3 years | |
Primary | Time course of dysautonomia symptoms | COMPASS31 scores (range: 0-100; 0 best-100 worst) | 3 years | |
Primary | Time course of orthostatic tolerance | Orthostatic tolerance (minutes) | 3 years |
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