Role of the Gut Microbiome in Complex Regional Pain Syndrome

NCT03612193 | Recruiting

• 1 other identifier: 201806182
• Study Type: observational
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this prospective, observational study is to determine the association between the composition of the gut microbiota and the severity and persistence of Complex Regional Pain Syndrome symptoms (Study A). The objective of Study B, a longitudinal study of microbiota biomarkers of patients with newly diagnosed CRPS is to determine if the researchers can predict which patients are more likely to recover compared to those who do not. A secondary objective of both studies is to examine cognitive flexibility in relation to outcomes (study A and B).

Conditions

Complex Regional Pain Syndromes

Outcome Measures

Primary Outcomes (2)

• Number of participants with taxonomic and metabolomic differences of the gut microbiome in relation to CRPS severity score

  Study A

  1 visit - up to one month

• Number of participants with taxonomic and metabolomic differences of the gut microbiome in relation to recovery from CRPS

  Study B

  12 months

Secondary Outcomes (3)

• Score results of the Stroop Color Word Test in relation to CRPS recovery

  12 months

• Logistic regression analysis for testing the association of CRPS severity score to weight in kilograms and height in meters aggregated to BMI (kilograms/meters squared)

  12 months

• Logistic regression analysis for testing the association of CRPS severity score to use of opioid analgesics

  12 months

Study Arms (5)

Study A: Chronic >1 year

Study A: Acute <1 year

Study A: Household Control

Study B: Newly Diagnosed <6 months

Study B: Household Controls

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Pain Management Center at Washington University/Barnes-Jewish Hospital medical campus

You may qualify if:

• Adults over the age of 18
• Current (\< 1 year duration) or former (\> 1 year) diagnosis of Complex Regional Pain Syndrome by the Budapest criteria
• English as primary language
• able to consent
• Adults over age of 18
• Cohabitant of person with current or former diagnosis of CRPS
• Study B: Longitudinal Study
• Adults over the age of 18
• Recent diagnosis (\<6 months) of Complex Regional Pain Syndrome by the Budapest criteria
• English as primary language
• able to consent
• Adults over age of 18
• Cohabitant of person with diagnosis of CRPS

You may not qualify if:

• Unwilling to participate in the study
• Lives alone
• Current use of probiotics and unwilling to stop for 1 week prior to stool sample
• Pregnant or lactating
• Vegan diet

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Related Publications (27)

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  PMID: 23811041 BACKGROUND

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  PMID: 24667741 BACKGROUND

• Weinstock LB, Myers TL, Walters AS, Schwartz OA, Younger JW, Chopra PJ, Guarino AH. Identification and Treatment of New Inflammatory Triggers for Complex Regional Pain Syndrome: Small Intestinal Bacterial Overgrowth and Obstructive Sleep Apnea. A A Case Rep. 2016 May 1;6(9):272-6. doi: 10.1213/XAA.0000000000000292.

  PMID: 26867023 BACKGROUND

• Fung TC, Olson CA, Hsiao EY. Interactions between the microbiota, immune and nervous systems in health and disease. Nat Neurosci. 2017 Feb;20(2):145-155. doi: 10.1038/nn.4476. Epub 2017 Jan 16.

  PMID: 28092661 BACKGROUND

• Cryan JF, Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci. 2012 Oct;13(10):701-12. doi: 10.1038/nrn3346. Epub 2012 Sep 12.

  PMID: 22968153 BACKGROUND

• Frank DN, Robertson CE, Hamm CM, Kpadeh Z, Zhang T, Chen H, Zhu W, Sartor RB, Boedeker EC, Harpaz N, Pace NR, Li E. Disease phenotype and genotype are associated with shifts in intestinal-associated microbiota in inflammatory bowel diseases. Inflamm Bowel Dis. 2011 Jan;17(1):179-84. doi: 10.1002/ibd.21339. Epub 2010 Sep 13.

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  PMID: 21683077 BACKGROUND

• Shen S, Lim G, You Z, Ding W, Huang P, Ran C, Doheny J, Caravan P, Tate S, Hu K, Kim H, McCabe M, Huang B, Xie Z, Kwon D, Chen L, Mao J. Gut microbiota is critical for the induction of chemotherapy-induced pain. Nat Neurosci. 2017 Sep;20(9):1213-1216. doi: 10.1038/nn.4606. Epub 2017 Jul 17.

  PMID: 28714953 BACKGROUND

• Amaral FA, Sachs D, Costa VV, Fagundes CT, Cisalpino D, Cunha TM, Ferreira SH, Cunha FQ, Silva TA, Nicoli JR, Vieira LQ, Souza DG, Teixeira MM. Commensal microbiota is fundamental for the development of inflammatory pain. Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2193-7. doi: 10.1073/pnas.0711891105. Epub 2008 Feb 11.

  PMID: 18268332 BACKGROUND

• Nayak RR, Turnbaugh PJ. Mirror, mirror on the wall: which microbiomes will help heal them all? BMC Med. 2016 May 4;14:72. doi: 10.1186/s12916-016-0622-6.

  PMID: 27146150 BACKGROUND

• Wang F, Meng J, Zhang L, Johnson T, Chen C, Roy S. Morphine induces changes in the gut microbiome and metabolome in a morphine dependence model. Sci Rep. 2018 Feb 26;8(1):3596. doi: 10.1038/s41598-018-21915-8.

  PMID: 29483538 BACKGROUND

• Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell. 2009 Oct 16;139(2):267-84. doi: 10.1016/j.cell.2009.09.028.

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• Powell N, Walker MM, Talley NJ. The mucosal immune system: master regulator of bidirectional gut-brain communications. Nat Rev Gastroenterol Hepatol. 2017 Mar;14(3):143-159. doi: 10.1038/nrgastro.2016.191. Epub 2017 Jan 18.

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• Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG, Bienenstock J, Cryan JF. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):16050-5. doi: 10.1073/pnas.1102999108. Epub 2011 Aug 29.

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• Neuman H, Debelius JW, Knight R, Koren O. Microbial endocrinology: the interplay between the microbiota and the endocrine system. FEMS Microbiol Rev. 2015 Jul;39(4):509-21. doi: 10.1093/femsre/fuu010. Epub 2015 Feb 19.

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• Lyte M. Microbial endocrinology in the microbiome-gut-brain axis: how bacterial production and utilization of neurochemicals influence behavior. PLoS Pathog. 2013;9(11):e1003726. doi: 10.1371/journal.ppat.1003726. Epub 2013 Nov 14. No abstract available.

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• Lyte M. Microbial endocrinology: Host-microbiota neuroendocrine interactions influencing brain and behavior. Gut Microbes. 2014 May-Jun;5(3):381-9. doi: 10.4161/gmic.28682. Epub 2014 Apr 1.

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• Nair AT, Ramachandran V, Joghee NM, Antony S, Ramalingam G. Gut Microbiota Dysfunction as Reliable Non-invasive Early Diagnostic Biomarkers in the Pathophysiology of Parkinson's Disease: A Critical Review. J Neurogastroenterol Motil. 2018 Jan 30;24(1):30-42. doi: 10.5056/jnm17105.

  PMID: 29291606 BACKGROUND

• Nagy-Szakal D, Williams BL, Mishra N, Che X, Lee B, Bateman L, Klimas NG, Komaroff AL, Levine S, Montoya JG, Peterson DL, Ramanan D, Jain K, Eddy ML, Hornig M, Lipkin WI. Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome. Microbiome. 2017 Apr 26;5(1):44. doi: 10.1186/s40168-017-0261-y.

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• Dinsdale EA, Edwards RA, Hall D, Angly F, Breitbart M, Brulc JM, Furlan M, Desnues C, Haynes M, Li L, McDaniel L, Moran MA, Nelson KE, Nilsson C, Olson R, Paul J, Brito BR, Ruan Y, Swan BK, Stevens R, Valentine DL, Thurber RV, Wegley L, White BA, Rohwer F. Functional metagenomic profiling of nine biomes. Nature. 2008 Apr 3;452(7187):629-32. doi: 10.1038/nature06810. Epub 2008 Mar 12.

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• Harden RN, Maihofner C, Abousaad E, Vatine JJ, Kirsling A, Perez RSGM, Kuroda M, Brunner F, Stanton-Hicks M, Marinus J, van Hilten JJ, Mackey S, Birklein F, Schlereth T, Mailis-Gagnon A, Graciosa J, Connoly SB, Dayanim D, Massey M, Frank H, Livshitz A, Bruehl S. A prospective, multisite, international validation of the Complex Regional Pain Syndrome Severity Score. Pain. 2017 Aug;158(8):1430-1436. doi: 10.1097/j.pain.0000000000000927.

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• 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.

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• Crock LW, Rodgers R, Huck NA, Schriefer LA, Lawrence D, Wang L, Muwanga GPB, Tawfik VL, Baldridge MT. Chronic pain and complex regional pain syndrome are associated with alterations to the intestinal microbiota in both humans and mice. An observational cross-sectional study. Neurobiol Pain. 2024 Nov 25;16:100173. doi: 10.1016/j.ynpai.2024.100173. eCollection 2024 Jul-Dec.

  PMID: 39670171 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Taxonomic and metabolomic biomarkers

MeSH Terms

Conditions

Complex Regional Pain Syndromes

Condition Hierarchy (Ancestors)

Autonomic Nervous System Diseases; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases

Study Officials

• Lara Crock, MD PhD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lara Crock, MD PhD

CONTACT

314-546-3882; crockl@wustl.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2018
• First Posted: August 2, 2018
• Study Start: December 19, 2018
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: November 5, 2025

Record last verified: 2025-11

Locations

US (1)