Clinical trial NCT03667404: Resistant Maltodextrin for Gut Microbiome in Parkinson's Disease: Safety and Tolerability Study
Official title: Gut Microbial Remodeling with Resistant Maltodextrin for Motor and Non-motor Symptoms in Parkinson's Disease: Safety and Tolerability Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Parkinson Disease
Intestinal Bacteria Flora Disturbance
Dietary Modification
Keywords: Resistant maltodextrin
dietary fiber
gut microbiome
Parkinson's disease
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: University of Illinois at Chicago
First posted: 2018-09-12
Enrollment: 30
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double blind placebo (maltodextrin) controlled randomized trial
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety and tolerability of a dietary fiber, resistant maltodextrin, in people with Parkinson's disease. It will also evaluate the fiber's effect on the gut microbiome and potential effects on motor function and non-motor functions. Half of the participants will receive resistant maltodextrin and the other half will receive a control substance, maltodextrin.

Detailed description: Intestinal microbiota may play in important role in Parkinson's disease (PD). Colonic bacteria play roles in multiple functions including gut motility and secretion of metabolites which can have systemic effects on the body. Recent evidence has shown that people with PD have an altered distribution of gut bacteria that healthy controls. These changes are associated with differences in various metabolites, including butyrate, that are involved in maintaining the gut barrier integrity and even gait and balance function. Microbiota dysbiosis could potentially exacerbate or even contribute to the pathogenesis of PD. Probiotic and dietary interventions may improve gut function and the motor symptoms in PD, but neither have been examined for their effect on the gut microbiome. Prebiotic treatments have been shown to order the microbiome in some populations, but have not been assessed for tolerability or efficacy in PD.

The objective of this study is to examine the safety and tolerability of resistant maltodextrin (RM), a prebiotic non-digestible fiber, and its effect on the microbiome and motor in non-motor symptoms and PD. The investigators will conduct a randomized, parallel-group double-blinded controlled trial assessing RM 50 g daily compared to maltodextrin (an easily digestible glucose polysaccharide) over 4 weeks. Patients will be dosed with 25 g daily for 1 week and then titrated to 50 g daily for the remaining 3 weeks.

The goals of this study include: 1) To determine the safety and tolerability of RM compared to maltodextrin in patients with PD; 2) To determine if RM will remodel the gut microbiome in patients with PD; 3) (exploratory) To determine if RM administration will improve motor and non-motor symptoms in PD.

Eligibility criteria: Inclusion Criteria:

* Men and women age ≥60 years
* Diagnosis of PD based on United Kingdom PD brain bank criteria, Hoehn and Yahr stage 1-3.
* Stable dose of PD medications for 30 days prior to study and for duration of study
* If used, stable dose of melatonin, sedative/hypnotic or stimulant medications

Exclusion Criteria:

* use of other prebiotic or probiotic treatment for 30 days prior to or during the study
* unstable medical or psychiatric disorder
* history of diabetes mellitus or current use of medication for diabetes
* cognitive impairment based on Montreal Cognitive Assessment (MoCA) \<25.
* current or recent (within previous 3 weeks) use of laxatives
* use of antibiotics in the past 30 days
* participation in another clinical trial in the past 30 days.

Primary outcomes:
measure: Adverse events
timeFrame: 4 weeks
Secondary outcomes:
measure: Gut microbial remodeling
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
Study officials:
affiliation: Northwestern Feinberg School of Medicine Department of Neurology
name: Roneil G Malkani
role: PRINCIPAL_INVESTIGATOR
References:
citation: Baer DJ, Stote KS, Henderson T, Paul DR, Okuma K, Tagami H, Kanahori S, Gordon DT, Rumpler WV, Ukhanova M, Culpepper T, Wang X, Mai V. The metabolizable energy of dietary resistant maltodextrin is variable and alters fecal microbiota composition in adult men. J Nutr. 2014 Jul;144(7):1023-9. doi: 10.3945/jn.113.185298. Epub 2014 Apr 17.
citation: Braak H, Rub U, Gai WP, Del Tredici K. Idiopathic Parkinson's disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J Neural Transm (Vienna). 2003 May;110(5):517-36. doi: 10.1007/s00702-002-0808-2.
citation: Cassani E, Privitera G, Pezzoli G, Pusani C, Madio C, Iorio L, Barichella M. Use of probiotics for the treatment of constipation in Parkinson's disease patients. Minerva Gastroenterol Dietol. 2011 Jun;57(2):117-21.
citation: Fastinger ND, Karr-Lilienthal LK, Spears JK, Swanson KS, Zinn KE, Nava GM, Ohkuma K, Kanahori S, Gordon DT, Fahey GC Jr. A novel resistant maltodextrin alters gastrointestinal tolerance factors, fecal characteristics, and fecal microbiota in healthy adult humans. J Am Coll Nutr. 2008 Apr;27(2):356-66. doi: 10.1080/07315724.2008.10719712.
citation: Forsyth CB, Shannon KM, Kordower JH, Voigt RM, Shaikh M, Jaglin JA, Estes JD, Dodiya HB, Keshavarzian A. Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson's disease. PLoS One. 2011;6(12):e28032. doi: 10.1371/journal.pone.0028032. Epub 2011 Dec 1.
citation: Hawkes CH, Del Tredici K, Braak H. Parkinson's disease: a dual-hit hypothesis. Neuropathol Appl Neurobiol. 2007 Dec;33(6):599-614. doi: 10.1111/j.1365-2990.2007.00874.x. Epub 2007 Oct 24.
citation: He B, Nohara K, Ajami NJ, Michalek RD, Tian X, Wong M, Losee-Olson SH, Petrosino JF, Yoo SH, Shimomura K, Chen Z. Transmissible microbial and metabolomic remodeling by soluble dietary fiber improves metabolic homeostasis. Sci Rep. 2015 Jun 4;5:10604. doi: 10.1038/srep10604.
citation: Holmqvist S, Chutna O, Bousset L, Aldrin-Kirk P, Li W, Bjorklund T, Wang ZY, Roybon L, Melki R, Li JY. Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats. Acta Neuropathol. 2014 Dec;128(6):805-20. doi: 10.1007/s00401-014-1343-6. Epub 2014 Oct 9.
citation: Keshavarzian A, Green SJ, Engen PA, Voigt RM, Naqib A, Forsyth CB, Mutlu E, Shannon KM. Colonic bacterial composition in Parkinson's disease. Mov Disord. 2015 Sep;30(10):1351-60. doi: 10.1002/mds.26307. Epub 2015 Jul 16.
citation: Kishimoto Y, Kanahori S, Sakano K, Ebihara S. The maximum single dose of resistant maltodextrin that does not cause diarrhea in humans. J Nutr Sci Vitaminol (Tokyo). 2013;59(4):352-7. doi: 10.3177/jnsv.59.352.
citation: Lee A, Gilbert RM. Epidemiology of Parkinson Disease. Neurol Clin. 2016 Nov;34(4):955-965. doi: 10.1016/j.ncl.2016.06.012. Epub 2016 Aug 18.
citation: Li S, Wang Y, Wang F, Hu LF, Liu CF. A New Perspective for Parkinson's Disease: Circadian Rhythm. Neurosci Bull. 2017 Feb;33(1):62-72. doi: 10.1007/s12264-016-0089-7. Epub 2016 Dec 19.
citation: Martinez-Martin P. The importance of non-motor disturbances to quality of life in Parkinson's disease. J Neurol Sci. 2011 Nov 15;310(1-2):12-6. doi: 10.1016/j.jns.2011.05.006. Epub 2011 May 31.
citation: Miyazato S, Kishimoto Y, Takahashi K, Kaminogawa S, Hosono A. Continuous intake of resistant maltodextrin enhanced intestinal immune response through changes in the intestinal environment in mice. Biosci Microbiota Food Health. 2016;35(1):1-7. doi: 10.12938/bmfh.2015-009. Epub 2015 Aug 25.
citation: Nagahara AH, Tuszynski MH. Potential therapeutic uses of BDNF in neurological and psychiatric disorders. Nat Rev Drug Discov. 2011 Mar;10(3):209-19. doi: 10.1038/nrd3366.
citation: Pan-Montojo F, Schwarz M, Winkler C, Arnhold M, O'Sullivan GA, Pal A, Said J, Marsico G, Verbavatz JM, Rodrigo-Angulo M, Gille G, Funk RH, Reichmann H. Environmental toxins trigger PD-like progression via increased alpha-synuclein release from enteric neurons in mice. Sci Rep. 2012;2:898. doi: 10.1038/srep00898. Epub 2012 Nov 30.
citation: Perez-Pardo P, de Jong EM, Broersen LM, van Wijk N, Attali A, Garssen J, Kraneveld AD. Promising Effects of Neurorestorative Diets on Motor, Cognitive, and Gastrointestinal Dysfunction after Symptom Development in a Mouse Model of Parkinson's Disease. Front Aging Neurosci. 2017 Mar 20;9:57. doi: 10.3389/fnagi.2017.00057. eCollection 2017.
citation: Queipo-Ortuno MI, Seoane LM, Murri M, Pardo M, Gomez-Zumaquero JM, Cardona F, Casanueva F, Tinahones FJ. Gut microbiota composition in male rat models under different nutritional status and physical activity and its association with serum leptin and ghrelin levels. PLoS One. 2013 May 28;8(5):e65465. doi: 10.1371/journal.pone.0065465. Print 2013.
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: Savignac HM, Corona G, Mills H, Chen L, Spencer JP, Tzortzis G, Burnet PW. Prebiotic feeding elevates central brain derived neurotrophic factor, N-methyl-D-aspartate receptor subunits and D-serine. Neurochem Int. 2013 Dec;63(8):756-64. doi: 10.1016/j.neuint.2013.10.006. Epub 2013 Oct 16.
citation: Scheperjans F, Aho V, Pereira PA, Koskinen K, Paulin L, Pekkonen E, Haapaniemi E, Kaakkola S, Eerola-Rautio J, Pohja M, Kinnunen E, Murros K, Auvinen P. Gut microbiota are related to Parkinson's disease and clinical phenotype. Mov Disord. 2015 Mar;30(3):350-8. doi: 10.1002/mds.26069. Epub 2014 Dec 5.
citation: Tandberg E, Larsen JP, Karlsen K. A community-based study of sleep disorders in patients with Parkinson's disease. Mov Disord. 1998 Nov;13(6):895-9. doi: 10.1002/mds.870130606.
citation: Thaiss CA, Zeevi D, Levy M, Zilberman-Schapira G, Suez J, Tengeler AC, Abramson L, Katz MN, Korem T, Zmora N, Kuperman Y, Biton I, Gilad S, Harmelin A, Shapiro H, Halpern Z, Segal E, Elinav E. Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis. Cell. 2014 Oct 23;159(3):514-29. doi: 10.1016/j.cell.2014.09.048. Epub 2014 Oct 16.
citation: Tomlinson CL, Stowe R, Patel S, Rick C, Gray R, Clarke CE. Systematic review of levodopa dose equivalency reporting in Parkinson's disease. Mov Disord. 2010 Nov 15;25(15):2649-53. doi: 10.1002/mds.23429.
citation: Unger MM, Moller JC, Mankel K, Eggert KM, Bohne K, Bodden M, Stiasny-Kolster K, Kann PH, Mayer G, Tebbe JJ, Oertel WH. Postprandial ghrelin response is reduced in patients with Parkinson's disease and idiopathic REM sleep behaviour disorder: a peripheral biomarker for early Parkinson's disease? J Neurol. 2011 Jun;258(6):982-90. doi: 10.1007/s00415-010-5864-1. Epub 2010 Dec 24.
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.
citation: Wallace CJK, Milev R. The effects of probiotics on depressive symptoms in humans: a systematic review. Ann Gen Psychiatry. 2017 Feb 20;16:14. doi: 10.1186/s12991-017-0138-2. eCollection 2017.