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

NCT01993680 | Completed Phase 2 DMC

• 1 other identifier: KEK-ZH-NR. 2011-0358
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Autonomic Disturbances in Parkinson's Disease

Outcome Measures

Primary Outcomes (2)

• Changes in diastolic blood pressure drop on Schellong manoeuvre

  10min standing, 10 min supine

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

  within 4h after test meal

Secondary Outcomes (3)

• Efficacy of Pyridostigmine bromide

  assess symptom severity for last 14 days

• Efficacy of Pyridostigmine bromide

  assess symptom severity for last 14 days

• Safety & Tolerability of Pyridostigmine bromide

  assess symptom severity for last 14 days

Study Arms (2)

Pyridostigmine bromide

EXPERIMENTAL

14 days of active treatment followed by 21 days wash out

Drug: Pyridostigmine bromide

fludrocortisone

ACTIVE COMPARATOR

14 days of fludrocortisone treatment; 21 days wash out

Drug: fludrocortisone

Interventions

Pyridostigmine bromide DRUG

Drug doses during the trial: Pyridostigmine bromide: 30mg p.o. 1-1-1 to 2-2-2 given for 14 days

Also known as: Mestinon

Pyridostigmine bromide

fludrocortisone DRUG

drug dose during the trial Fludrocortisone: 0,1mg p.o. 1-0-0 to 2-0-0 given for 14 days

Also known as: florinef

fludrocortisone

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• informed, written \& formal consent for participation
• male / female subjects, aged 50-80 years
• PD patients (18 subjects with symptomatic orthostatic hypotension)

You may not qualify if:

• 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

Sponsors & Collaborators

• Christian Baumann: lead

Study Sites (1)

University Hospital Zurich, Division of Neurology

Zurich, Canton of Zurich, 8091, Switzerland

Location

Related Publications (3)

• 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. doi: 10.1097/01.wnp.0000229946.01494.4c.

  PMID: 17016160 BACKGROUND

• 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. doi: 10.1007/s10286-005-0225-3.

  PMID: 15768203 BACKGROUND

• Schreglmann SR, Buchele F, Sommerauer M, Epprecht L, Kagi G, Hagele-Link S, Gotze O, Zimmerli L, Waldvogel D, Baumann CR. Pyridostigmine bromide versus fludrocortisone in the treatment of orthostatic hypotension in Parkinson's disease - a randomized controlled trial. Eur J Neurol. 2017 Apr;24(4):545-551. doi: 10.1111/ene.13260. Epub 2017 Feb 22.

  PMID: 28224720 DERIVED

MeSH Terms

Interventions

Pyridostigmine Bromide; Fludrocortisone; fludrocortisone acetate

Intervention Hierarchy (Ancestors)

Pyridinium Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrocortisone; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Christian Baumann, MD

  University Hospital Zurich, Division of Neurology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor dr. med.

Study Record Dates

• First Submitted: April 27, 2012
• First Posted: November 25, 2013
• Study Start: June 1, 2012
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2016
• Last Updated: January 25, 2021

Record last verified: 2021-01

Locations

CH (1)