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

NCT ID: NCT05787756

Last Updated: 2023-04-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

80 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-01-01

Study Completion Date

2023-10-30

Brief Summary

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

Detailed Description

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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.

Conditions

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Parkinson Disease

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Parkinson disease

Participants with newly diagnosed Parkinson's disease

No interventions assigned to this group

Control Subjects

Control subjects - will be selected from household/spousal contacts of the participants with Parkinson's disease

No interventions assigned to this group

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

110 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Biomathematics & Statistics Scotland (BioSS)

UNKNOWN

Sponsor Role collaborator

NHS Grampian

OTHER_GOV

Sponsor Role collaborator

University of Aberdeen

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Isobel JM Sleeman, BMBCh, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Aberdeen

Locations

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Human Nutrition Unit, Rowett Institute, University of Aberdeen

Aberdeen, Aberdeen City, United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Isobel JM Sleeman, BMBCh, PhD

Role: CONTACT

07471234054

Angus Macleod, MBChB, PhD

Role: CONTACT

01224 437120

Facility Contacts

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Isobel J Sleeman, BMBCh, PhD

Role: primary

07471234054

Angus Macleod, MBBS, PhD

Role: backup

01224437120

References

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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.

Reference Type BACKGROUND
PMID: 21130017 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 35045378 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24240814 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18676172 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17588237 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12677732 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27912057 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29454662 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27591074 (View on PubMed)

Other Identifiers

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2-048-21

Identifier Type: -

Identifier Source: org_study_id

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