Clinical trial NCT05787756: Constipation and Changes in the Gut Flora in Parkinson's Disease
Official title: Constipation and Changes in the Gut Flora in Parkinson's Disease: a Pilot Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Parkinson Disease
Lead sponsor: University of Aberdeen
Sponsor class: OTHER
Collaborators: name: Biomathematics & Statistics Scotland (BioSS)
name: NHS Grampian
First posted: 2023-03-28
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 110
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Parkinson disease group: potential participants will be invited into the study if they have recently been diagnosed with Parkinson's disease and have not yet started medication for the condition

Control group: spouses or other household contacts will be invited to the study

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Micro-organism prevalence in stool sample
timeFrame: Baseline
measure: Micro-organism prevalence in stool sample
timeFrame: Within two months of baseline
Secondary outcomes:
measure: Analysis of stool samples for concentration of short chain fatty acids
timeFrame: Baseline
measure: Analysis of stool samples for concentration of calprotectin
timeFrame: Baseline
measure: Analysis of stool samples for markers of gut function (short chain fatty acids and calprotectin)
timeFrame: Within two months of the baseline sample
measure: To assess the extent of swallowing problems (dysphagia) by a questionnaire
timeFrame: Baseline
measure: To assess the extent of swallowing problems using a standardized swallowing test
timeFrame: Baseline
measure: To assess the extent of swallowing problems using a standardized swallowing test
timeFrame: Four weeks after the baseline assessment
measure: To assess taste sensation using a simple test
timeFrame: Baseline
measure: To assess dietary intake over a 24 hour period using a structured interview
timeFrame: Baseline
measure: To assess the reliability of bio-impedence analysis in determining fat mass in older adults with and without PD
timeFrame: Baseline
measure: To assess the reliability of bio-impedence analysis in determining fat mass in older adults
timeFrame: Four weeks after baseline assessment
measure: To assess the reliability of bio-impedence analysis in determining fat mass in older adults
timeFrame: Baseline
measure: To assess the reliability of bio-impedence analysis in determining fat mass in older adults
timeFrame: Four weeks after the baseline assessment
Other outcomes:
Locations:
city: Aberdeen
country: United Kingdom
facility: Human Nutrition Unit, Rowett Institute, University of Aberdeen
state: Aberdeen City
Study officials:
affiliation: University of Aberdeen
name: Isobel JM Sleeman, BMBCh, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
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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.
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.
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.
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.
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.