Tenapanor in Synucleinopathy-Related Constipation

Parkinson's Disease Clinical Trial

Official title:

Efficacy and Safety of Tenapanor in Synucleinopathy-Related Constipation

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06460038
• Other study ID #: 2405-21279
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: December 2024
• Est. completion date: March 2026

Study information

• Verified date: June 2024
• Source: Cedar Valley Digestive Health Center
• Contact: Richard A. Manfready, MD, AM, FACP
• Phone: (319) 235-5390
• Email: rman[@]alum.mit.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Investigation of tenapanor as a potential treatment for synucleinopathy-associated constipation

Description:

Randomized, double-blind, placebo controlled trial of tenapanor vs. placebo for treating synucleinopathy-associated constipation in Parkinson's disease.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: March 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 89 Years

Eligibility

Inclusion Criteria:

• To be considered for inclusion, subjects of all sexes must be between the ages of 50 and 89 years. Patients of child-bearing potential must agree to use appropriate methods of contraception, be post-menopausal or sterile. Subjects must meet the diagnosis of PD (with active disease within Hoehn and Yahr stages 1-3) as diagnosed by a neurologist according to criteria set forth by the International Parkinson and Movement Disorder Society, of which our investigators are members and contributors.

• In the 6 months prior to screening, included patients must report average weekly stool frequency of 5 or fewer spontaneous bowel movements (SBMs) with 2 or fewer complete spontaneous bowel movements (CSBMs) with sensation of complete evacuation, and must have an average weekly stool consistency of 3 or less using the Bristol Stool Form Scale (BSFS). Over-the-counter laxative use is permitted as needed at baseline and during the course of the study (includes PEG solutions, senokot, bisacodyl, and magnesium)

Exclusion Criteria:

• General exclusion criteria are functional diarrhea, IBS-D/M as defined by Rome IV Criteria, symptomatic structural abnormality of the GI tract, inflammatory bowel disease, hepatic dysfunction (ALT or AST = 2.5x the upper limit of normal), renal impairment (serum creatinine >2mg/dl), pregnancy, lactation, and presence of significant disease that will limit participation within the 6 months before screening. Patients will also be excluded if they have dyssynergic defecation, diagnosed clinically or by anorectal manometry as failure to relax or inappropriate contraction of the puborectalis and external anal sphincter muscles as pressure increases in the rectum.

• Use of prescription laxatives (ie. linaclotide, naloxegol, lubiprostone).

Related Conditions & MeSH terms

• Constipation
• Parkinson Disease
• Parkinson's Disease
• Synucleinopathy

Intervention

Drug:
• Tenapanor
Inhibitor of NH3
• Placebo
Placebo drug

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Cedar Valley Digestive Health Center	Ardelyx

References & Publications (7)

Chey WD, Lembo AJ, Rosenbaum DP. Efficacy of Tenapanor in Treating Patients With Irritable Bowel Syndrome With Constipation: A 12-Week, Placebo-Controlled Phase 3 Trial (T3MPO-1). Am J Gastroenterol. 2020 Feb;115(2):281-293. doi: 10.14309/ajg.0000000000000516. — View Citation

Chey WD, Lembo AJ, Rosenbaum DP. Tenapanor Treatment of Patients With Constipation-Predominant Irritable Bowel Syndrome: A Phase 2, Randomized, Placebo-Controlled Efficacy and Safety Trial. Am J Gastroenterol. 2017 May;112(5):763-774. doi: 10.1038/ajg.2017.41. Epub 2017 Feb 28. — View Citation

Chey WD, Lembo AJ, Yang Y, Rosenbaum DP. Efficacy of Tenapanor in Treating Patients With Irritable Bowel Syndrome With Constipation: A 26-Week, Placebo-Controlled Phase 3 Trial (T3MPO-2). Am J Gastroenterol. 2021 Jun 1;116(6):1294-1303. doi: 10.14309/ajg.0000000000001056. — View Citation

Hall DA, Voigt RM, Cantu-Jungles TM, Hamaker B, Engen PA, Shaikh M, Raeisi S, Green SJ, Naqib A, Forsyth CB, Chen T, Manfready R, Ouyang B, Rasmussen HE, Sedghi S, Goetz CG, Keshavarzian A. An open label, non-randomized study assessing a prebiotic fiber intervention in a small cohort of Parkinson's disease participants. Nat Commun. 2023 Feb 18;14(1):926. doi: 10.1038/s41467-023-36497-x. — View Citation

Manfready RA, Engen PA, Verhagen Metman L, Sanzo G, Goetz CG, Hall DA, Forsyth CB, Raeisi S, Voigt RM, Keshavarzian A. Attenuated Postprandial GLP-1 Response in Parkinson's Disease. Front Neurosci. 2021 Jul 2;15:660942. doi: 10.3389/fnins.2021.660942. eCollection 2021. — View Citation

Manfready RA, Forsyth CB, Voigt RM, Hall DA, Goetz CG, Keshavarzian A. Gut-Brain Communication in Parkinson's Disease: Enteroendocrine Regulation by GLP-1. Curr Neurol Neurosci Rep. 2022 Jul;22(7):335-342. doi: 10.1007/s11910-022-01196-5. Epub 2022 May 28. — View Citation

Post Z, Manfready RA, Keshavarzian A. Overview of the Gut-Brain Axis: From Gut to Brain and Back Again. Semin Neurol. 2023 Aug;43(4):506-517. doi: 10.1055/s-0043-1771464. Epub 2023 Aug 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete spontaneous bowel movements (CSBM)	Our primary endpoint will be CSBM response, defined as an increase of at least one CSBM per week compared to baseline for at least 6 of the 12 treatment weeks. A CSBM is defined as a bowel movement that occurs naturally and is accompanied by a feeling of complete evacuation	6 of 12 weeks
Secondary	Abdominal pain and bloating response	Decrease in severity score of at least 20% or more from baseline in 6 of 12 weeks	6 of 12 weeks
Secondary	GIDS-PD	GIDS-PD improvement of 20%, where score ranges 1-108, or a 20% improvement in constipation, bowel irritability, or upper GI subscores	Week 12
Secondary	Calprotectin	Decrease in fecal calprotectin by 20% or greater	Week 12
Secondary	Lipopolysaccharide binding protein	Decrease in serum lipopolysaccharide binding protein by 20%	Week 12
Secondary	Movement symptoms	MDS-UPDRS total improvement by 20% compared to baseline	Week 12
Secondary	CSBM continuous	CSBM treated as a continuous variable. We expect an increase of CSBMs in the treatment group compared to the placebo group.	Week 12