Orthostatic Dysregulation and Associated Gastrointestinal Dysfunction in Parkinson's Disease -Treatment
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|ClinicalTrials.gov Identifier: NCT01993680|
Recruitment Status : Unknown
Verified September 2015 by University of Zurich.
Recruitment status was: Active, not recruiting
First Posted : November 25, 2013
Last Update Posted : September 30, 2015
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.
|Condition or disease||Intervention/treatment||Phase|
|Autonomic Disturbances in Parkinson's Disease||Drug: Pyridostigmine bromide Drug: fludrocortisone||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Double (Participant, Investigator)|
|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 Start Date :||June 2012|
|Actual Primary Completion Date :||April 2015|
|Estimated Study Completion Date :||January 2016|
Experimental: Pyridostigmine bromide
14 days of active treatment followed by 21 days wash out
Drug: Pyridostigmine bromide
Drug doses during the trial:
Pyridostigmine bromide: 30mg p.o. 1-1-1 to 2-2-2 given for 14 days
Other Name: Mestinon
Active Comparator: fludrocortisone
14 days of fludrocortisone treatment; 21 days wash out
drug dose during the trial Fludrocortisone: 0,1mg p.o. 1-0-0 to 2-0-0 given for 14 days
Other Name: florinef
- Changes in diastolic blood pressure drop on Schellong manoeuvre [ Time Frame: 10min standing, 10 min supine ]
- Changes in half emptying time t50 on 13C-sodium octanoate breath test [ Time Frame: within 4h after test meal ]
- Efficacy of Pyridostigmine bromide [ Time Frame: assess symptom severity for last 14 days ]central blood pressure, heart rate variability and pulse wave velocity
- Efficacy of Pyridostigmine bromide [ Time Frame: assess symptom severity for last 14 days ]Motor functions (UPDRS III), frequency and subjective quality of defecation, frequency and urgency of micturition, tremor severity (Whiget tremor scale);
- Safety & Tolerability of Pyridostigmine bromide [ Time Frame: assess symptom severity for last 14 days ]subjective assessment of sialorrhea, Hospital Anxiety and Depression Scale, Montreal Cognitive Assessment;
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01993680
|University Hospital Zurich, Division of Neurology|
|Zurich, ZH, Switzerland, 8091|
|Principal Investigator:||Christian Baumann, MD||University Hospital Zurich, Division of Neurology|