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Orthostatic Dysregulation and Associated Gastrointestinal Dysfunction in Parkinson's Disease -Treatment

Information source: University of Zurich
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Autonomic Disturbances in Parkinson`s Disease

Intervention: Pyridostigmine bromide (Drug); fludrocortisone (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: University of Zurich

Official(s) and/or principal investigator(s):
Christian Baumann, MD, Principal Investigator, Affiliation: University Hospital Zurich, Division of Neurology

Overall contact:
Sebastian Schreglmann, MD, Phone: +41 (0)44 255 11 11, Email: sebastian.schreglmann@usz.ch


Disabling symptoms of blood pressure dysregulation, impaired swallowing and digestion are common amongst Parkinson`s patients. So far the exact pathophysiology for this is not fully understood. There are results from pathological analyses that the autonomic nervous system is also affected by the accumulation of alpha-Synuclein and that this might even happen in very early stages of the disease process (Qualman et al., 1984; Wakabayashi et al., 1989; Wakabayashi et al., 1990; Bloch et al., 2006). Blood pressure dysregulation is a common autonomic symptom in Parkinson`s patients and

treatment - currently most often achieved with Fludrocortisone - often leads to supine

hypertension (Plaschke et al., 1998; Braune et al., 1999; Magerkurth et al., 2005). There are studies in patients with autonomic failure that indicate that Pyridostigmine bromide might be an alternative treatment option without causing disabling supine hypertension (Singer et al., 2003; Sandroni et al., 2005; Singer et al., 2006; Yamamoto et al., 2006). Delayed gastric emptying is also an autonomic symptom associated with Parkinson`s disease. By the elevation of the cholinergic tone with Pyridostigmine bromide the investigators also expect to alleviate symptoms of delayed gastric emptying and obstipation, possibly even facilitating the uptake of dopaminergic medication through the gut (Sadjadpour, 1983; Bharucha et al., 2008). Therefore the investigators designed a monocentric randomized, controlled, double blind, crossover phase II trial to show non-inferiority of the effect of pyridostigmine bromide vs. fludrocortisone on symptoms of autonomic dysregulation in Parkinson`s disease.

Clinical Details

Official title: A Monocentric Randomized, Controlled, Double Blind, Crossover Phase II Trial to Show Non-inferiority of the Effect of Pyridostigmine Bromide vs. Fludrocortisone on Symptoms of Autonomic Dysregulation in Parkinson`s Disease

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome:

Changes in diastolic blood pressure drop on Schellong manoeuvre

Changes in half emptying time t50 on 13C-sodium octanoate breath test

Secondary outcome:

Efficacy of Pyridostigmine bromide

Efficacy of Pyridostigmine bromide

Safety & Tolerability of Pyridostigmine bromide

Detailed description: In summary, investigators in recent years became more and more aware of the non-motor symptoms of PD and their impact on affected individuals. Therefore therapeutic strategies to ameliorate these symptoms are ever more needed. Sufficient clinical data for the treatment of symptoms of blood pressure dysregulation is still lacking. This study is aiming at closing this knowledge gap by comparing the efficacy and tolerability of a promising new agent, pyridostigmine bromide with the standard treatment, fludrocortisone. The proposed target of pyridostigmine in this respect is at the autonomic ganglion in the efferent limb of the baroreflex. Via a reduction of acetylcholine breakdown the sympathetic ganglionic transmission increases upon orthostatic stress (Singer et al., 2006). Via the same mechanism we aim to facilitate gastrooesophageal motility and gastric emptying: Both relaxation and contractibility of the oesophagus are known to be affected in PD patients as shown in a manometric study (Sung et al., 2010). Both relaxation and contractability are mainly influenced by nicotinergic and muscarinergic, cholinergic vagal efferents to the oesophagus (Chang et al., 2003). Via a reduction of acetylcholine breakdown we aim to increase the cholinergic tone and thereby normalize the reduced relaxation and contractibility. We also intent to show that this faster gastric transit results in a faster absorption of

Madopar into the bloodstream - we therefore will measure Levodopa and its metabolites during

the first 60mins after ingestion of 125mg fast-release Madopar in serial venous blood samples via high-pressure liquid chromatography.


Minimum age: 50 Years. Maximum age: 80 Years. Gender(s): Both.


Inclusion criteria:

- informed, written & formal consent for participation

- male / female subjects, aged 50-80 years

- PD patients (18 subjects with symptomatic orthostatic hypotension)

Exclusion criteria: - Antihypertensive treatment

- medication influencing gastrointestinal motility for at least the elimination half

life of the drug

- medication interfering with blood-pressure regulation for at least the elimination

half life of the drug

- significant systemic illness

- BMI <18 or >30kg/m2

- symptoms or a history of GI disease or surgery

- with any evidence of infectious disease

- evidence or history of drug or alcohol abuse

- diabetes mellitus

Locations and Contacts

Sebastian Schreglmann, MD, Phone: +41 (0)44 255 11 11, Email: sebastian.schreglmann@usz.ch

University Hospital Zurich, Division of Neurology, Zurich, ZH 8091, Switzerland; Recruiting
Additional Information

Related publications:

Singer W, Opfer-Gehrking TL, Nickander KK, Hines SM, Low PA. Acetylcholinesterase inhibition in patients with orthostatic intolerance. J Clin Neurophysiol. 2006 Oct;23(5):476-81.

Sandroni P, Opfer-Gehrking TL, Singer W, Low PA. Pyridostigmine for treatment of neurogenic orthostatic hypotension [correction of hypertension]--a follow-up survey study. Clin Auton Res. 2005 Feb;15(1):51-3.

Starting date: June 2012
Last updated: November 25, 2013

Page last updated: August 23, 2015

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