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

Parkinson Disease Clinical Trial

— GUT-PD  

Official title:

Constipation and Changes in the Gut Flora in Parkinson's Disease: a Pilot Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05787756
• Other study ID #: 2-048-21
• Status: Recruiting
• Start date: January 1, 2023
• Est. completion date: October 30, 2023

Study information

• Verified date: April 2023
• Source: University of Aberdeen
• Contact: Isobel JM Sleeman, BMBCh, PhD
• Phone: 07471234054
• Email: isobel.sleeman[@]abdn.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: October 30, 2023
• Est. primary completion date: August 30, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 110 Years

Eligibility

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.

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.

Related Conditions & MeSH terms

• Constipation
• Parkinson Disease

Locations

Country	Name	City	State
United Kingdom	Human Nutrition Unit, Rowett Institute, University of Aberdeen	Aberdeen	Aberdeen City

Sponsors (3)

Lead Sponsor	Collaborator
University of Aberdeen	Biomathematics & Statistics Scotland (BioSS), NHS Grampian

Country where clinical trial is conducted

United Kingdom, 

References & Publications (9)

De Pablo-Fernandez E, Gebeyehu GG, Flain L, Slater R, Frau A, Ijaz UZ, Warner T, Probert C. The faecal metabolome and mycobiome in Parkinson's disease. Parkinsonism Relat Disord. 2022 Feb;95:65-69. doi: 10.1016/j.parkreldis.2022.01.005. Epub 2022 Jan 13. — View Citation

Gage H, Kaye J, Kimber A, Storey L, Egan M, Qiao Y, Trend P. Correlates of constipation in people with Parkinson's. Parkinsonism Relat Disord. 2011 Feb;17(2):106-11. doi: 10.1016/j.parkreldis.2010.11.003. Epub 2010 Dec 3. — View Citation

Hilton D, Stephens M, Kirk L, Edwards P, Potter R, Zajicek J, Broughton E, Hagan H, Carroll C. Accumulation of alpha-synuclein in the bowel of patients in the pre-clinical phase of Parkinson's disease. Acta Neuropathol. 2014 Feb;127(2):235-41. doi: 10.1007/s00401-013-1214-6. Epub 2013 Nov 17. — View Citation

Jaffrin MY, Morel H. Body fluid volumes measurements by impedance: A review of bioimpedance spectroscopy (BIS) and bioimpedance analysis (BIA) methods. Med Eng Phys. 2008 Dec;30(10):1257-69. doi: 10.1016/j.medengphy.2008.06.009. Epub 2008 Aug 3. — View Citation

Manor Y, Giladi N, Cohen A, Fliss DM, Cohen JT. Validation of a swallowing disturbance questionnaire for detecting dysphagia in patients with Parkinson's disease. Mov Disord. 2007 Oct 15;22(13):1917-21. doi: 10.1002/mds.21625. — View Citation

Mueller C, Kallert S, Renner B, Stiassny K, Temmel AF, Hummel T, Kobal G. Quantitative assessment of gustatory function in a clinical context using impregnated "taste strips". Rhinology. 2003 Mar;41(1):2-6. — View Citation

Sampson TR, Debelius JW, Thron T, Janssen S, Shastri GG, Ilhan ZE, Challis C, Schretter CE, Rocha S, Gradinaru V, Chesselet MF, Keshavarzian A, Shannon KM, Krajmalnik-Brown R, Wittung-Stafshede P, Knight R, Mazmanian SK. Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease. Cell. 2016 Dec 1;167(6):1469-1480.e12. doi: 10.1016/j.cell.2016.11.018. — View Citation

Schwiertz A, Spiegel J, Dillmann U, Grundmann D, Burmann J, Fassbender K, Schafer KH, Unger MM. Fecal markers of intestinal inflammation and intestinal permeability are elevated in Parkinson's disease. Parkinsonism Relat Disord. 2018 May;50:104-107. doi: 10.1016/j.parkreldis.2018.02.022. Epub 2018 Feb 12. — View Citation

Unger MM, Spiegel J, Dillmann KU, Grundmann D, Philippeit H, Burmann J, Fassbender K, Schwiertz A, Schafer KH. Short chain fatty acids and gut microbiota differ between patients with Parkinson's disease and age-matched controls. Parkinsonism Relat Disord. 2016 Nov;32:66-72. doi: 10.1016/j.parkreldis.2016.08.019. Epub 2016 Aug 26. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Micro-organism prevalence in stool sample	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.	Baseline
Primary	Micro-organism prevalence in stool sample	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.	Within two months of baseline
Secondary	Analysis of stool samples for concentration of short chain fatty acids	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).	Baseline
Secondary	Analysis of stool samples for concentration of calprotectin	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).	Baseline
Secondary	Analysis of stool samples for markers of gut function (short chain fatty acids and calprotectin)	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.	Within two months of the baseline sample
Secondary	To assess the extent of swallowing problems (dysphagia) by a questionnaire	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	Baseline
Secondary	To assess the extent of swallowing problems using a standardized swallowing test	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.	Baseline
Secondary	To assess the extent of swallowing problems using a standardized swallowing test	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.	Four weeks after the baseline assessment
Secondary	To assess taste sensation using a simple test	Participants taste recognition will be assessed using standardized taste strips from Burghart (sweet, salty, sour and bitter)	Baseline
Secondary	To assess dietary intake over a 24 hour period using a structured interview	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.	Baseline
Secondary	To assess the reliability of bio-impedence analysis in determining fat mass in older adults with and without PD	Fat mass in kilograms will be measured using a seca mBCA 525 bio-impedence machine.	Baseline
Secondary	To assess the reliability of bio-impedence analysis in determining fat mass in older adults	Fat mass in kilograms will be measured using a seca mBCA 525 bio-impedence machine.	Four weeks after baseline assessment
Secondary	To assess the reliability of bio-impedence analysis in determining fat mass in older adults	Fat free mass in kilograms will be measured using a seca mBCA 525 bio-impedence machine.	Baseline
Secondary	To assess the reliability of bio-impedence analysis in determining fat mass in older adults	Fat free mass in kilograms will be measured using a seca mBCA 525 bio-impedence machine.	Four weeks after the baseline assessment