Constipation and Changes in the Gut Flora in Parkinson's Disease

Recruiting

• Conditions: Parkinson Disease

• Registration Number: NCT05787756
• Lead Sponsor: University of Aberdeen

Brief Summary

The aim of this study is to investigate the link between gut health and Parkinson's disease

Detailed Description

Parkinson's disease (PD) is a common, age-related neurological condition, affecting approximately 145,000 people in the United Kingdom. Diagnostic symptoms include stiffness, tremor, unsteadiness and slow movements. Interestingly, while PD is usually considered to be a neurological condition, pathological changes occur in the gut years before diagnosis, often causing constipation. As such, the gut has attracted attention as a possible therapeutic target.

Previous studies have shown different profiles of gut bacteria and the short chain fatty acids (SCFAs) they produce in people with PD. There is evidence these changes might be significant to the disease course, as faecal transplants from people with PD worsened symptoms in a mouse model of PD. The mechanism for this is unclear, but changes in SCFAs and gut wall inflammation, have both been suggested. Studies so far have compared gut bacteria in people with and without PD, however, as the healthy controls often don't have constipation, it is unclear if the differences seen are due to PD itself or the associated constipation.

This pilot study aims to determine differences in the frequency of gut micro-organisms (bacteria, fungi and archaea) and gut function, other than those caused by constipation. 40 participants with a new diagnosis of PD will be recruited from Movement Disorder clinics within National Health Service (NHS) Grampian. 40 healthy (non-PD) controls will be recruited from the PD participants households (whenever feasible). All 80 participants will be clinically assessed and asked to provide two stool samples. The samples will be analysed for the frequency of gut micro-organisms, changes in gut function (short chain fatty acid concentrations) and gut inflammation (calprotectin concentrations).

The aim of this pilot study is to determine the key differences in gut micro-organisms in PD compared to controls, which may have a role in disease progression. It is likely that the results of this proof of concept study would need to be confirmed in a larger study before the investigators are able to plan an intervention trial, such as testing a prebiotic product, with the aim of normalising gut micro-organisms, and potentially modifying the disease course.

Study Timeline

• Study Start: 2023-01-01
• Study First Submitted: 2023-03-01
• Study First Submitted QC: 2023-03-15
• Study First Posted: 2023-03-28
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-10
• Last Update Posted: 2023-04-12
• Primary Completion: 2023-08-30
• Study Completion: 2023-10-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

Participants with Parkinson's disease 2. Community-dwelling patients with newly diagnosed PD who have not yet started medication for Parkinson's disease.

Control Participants

1. Healthy (non-Parkinsonian) members of the participants household will be invited to act as controls.

Read More

Exclusion Criteria

1. Use of oral or intravenous antibiotics in the last 8 weeks.
2. Active gastrointestinal disease, not including constipation or irritable bowel syndrome without other symptoms.
3. Current use of medications which cause/worsen constipation e.g., opioids, tramadol, gabapentin, pregabalin.
4. Potential controls will be excluded if they report prodromal symptoms of PD, such as anosmia or rapid eye movement (REM) sleep disorder or display parkinsonian signs on examination.
5. Inability to give informed consent at any stage of the study e.g., because of dementia.

Read More

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Micro-organism prevalence in stool sample	Within two months of baseline	Stool samples will be posted to the Rowett Institute, and processed and analysed in the laboratory at The Rowett Institute, University of Aberdeen. The samples will be analysed for water content and microbial RNA/DNA will be extracted for genome analysis. When the analysis is complete, the faecal samples will be destroyed.

Secondary Outcome Measures

Name	Time	Method
Analysis of stool samples for concentration of short chain fatty acids	Baseline	Stool samples will be posted to the Rowett Institute via Royal Mail. Samples will be processed and analysed in the laboratory at The Rowett Institute, University of Aberdeen. The samples will be analysed for short chain fatty acid concentration (µmol/g).
Analysis of stool samples for concentration of calprotectin	Baseline	Stool samples will be posted to the Rowett Institute via Royal Mail. Samples will be processed and analysed in the laboratory at The Rowett Institute, University of Aberdeen. The samples will be analysed for short calprotectin concentration (µg/g).
To assess the reliability of bio-impedence analysis in determining fat mass in older adults with and without PD	Baseline	Fat mass in kilograms will be measured using a seca mBCA 525 bio-impedence machine.
To assess the reliability of bio-impedence analysis in determining fat mass in older adults	Four weeks after the baseline assessment	Fat free mass in kilograms will be measured using a seca mBCA 525 bio-impedence machine.
Analysis of stool samples for markers of gut function (short chain fatty acids and calprotectin)	Within two months of the baseline sample	Stool samples will be posted to the Rowett Institute via Royal Mail. Samples will be processed and analysed in the laboratory at The Rowett Institute, University of Aberdeen. The samples will be analysed for short chain fatty acid (SCFA) profile and calprotectin concentration. When the analysis is complete, the faecal samples will be destroyed.
To assess the extent of swallowing problems (dysphagia) by a questionnaire	Baseline	Participants will be asked to completed a standardized swallowing questionnaire (Swallowing Disturbance Questionnaire), which has been validated in people with Parkinson's disease. The score ranges from 0-43, with a higher score increasing the likelihood for a swallowing problem, which would require further investigation
To assess taste sensation using a simple test	Baseline	Participants taste recognition will be assessed using standardized taste strips from Burghart (sweet, salty, sour and bitter)
To assess dietary intake over a 24 hour period using a structured interview	Baseline	Following the initial visit, the participant will receive a phone call from a trained member of the team to perform a 24-hour dietary recall interview. This is a structured interview where participants are asked to recall all food and beverage consumption over a 24-hour period and further questions are asked to determine further details, including portion size and ingredients and cooking methods used. The whole interview usually takes 20 to 60 minutes.
To assess the extent of swallowing problems using a standardized swallowing test	Four weeks after the baseline assessment	Participants will be asked to drink 150 millilitres of cold water from a clear cup. The rater will sit at their side and record them on video for later analysis. The speed in ml/second and volume per average swallow will be recorded by determining if any residual volume is left, the number of seconds to complete the task and the number of swallows. The test will be terminated if there is any indication of aspiration of liquid.

Trial Locations

Locations (1)

Human Nutrition Unit, Rowett Institute, University of Aberdeen; 🇬🇧 Aberdeen, Aberdeen City, United Kingdom