Clinical trial NCT06460038: Tenapanor in Synucleinopathy-Related Constipation
Official title: Efficacy and Safety of Tenapanor in Synucleinopathy-Related Constipation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Synucleinopathy
Parkinson's Disease
Keywords: tenapanor
synucleinopathy
Parkinson's disease
constipation
Lead sponsor: Cedar Valley Digestive Health Center
Sponsor class: OTHER
Collaborators: name: Ardelyx
First posted: 2024-06-14
Enrollment: 30
Sex: ALL
Minimum age (years): 50
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, placebo controlled trial of tenapanor vs. placebo
Primary purpose: TREATMENT

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

Detailed description: Randomized, double-blind, placebo controlled trial of tenapanor vs. placebo for treating synucleinopathy-associated constipation in Parkinson\&#39;s disease.

Eligibility criteria: Inclusion Criteria

1. Age 50-89 years.
2. Diagnosis of PD within Hoehn and Yahr stages 1-3, confirmed by a neurologist per International Parkinson and Movement Disorder Society criteria.
3. Average weekly stool frequency of ≤5 spontaneous bowel movements (SBMs) and ≤2 complete spontaneous bowel movements (CSBMs) over the past 6 months. These criteria will be verified during a 2-week screening period.
4. Stool consistency ≤3 on the Bristol Stool Form Scale (BSFS). This criterion will be verified during a 2-week screening period.
5. Agreement to use contraception, if applicable.

Exclusion Criteria

1. Functional diarrhea or IBS-D/M based on Rome IV Criteria.
2. Symptomatic structural GI abnormalities or inflammatory bowel disease.
3. Significant hepatic (ALT or AST ≥ 2.5x the upper limit of normal) or renal (serum creatinine \>2mg/dl) dysfunction.
4. Pregnancy or lactation.
5. Diagnosis of primary dyssynergic defecation by anorectal manometry.

Primary outcomes:
measure: Complete spontaneous bowel movements (CSBM)
timeFrame: 6 of 12 weeks
Secondary outcomes:
measure: Abdominal pain and bloating response
timeFrame: 6 of 12 weeks
measure: Calprotectin
timeFrame: Week 12
measure: Lipopolysaccharide binding protein
timeFrame: Week 12
measure: Complete spontaneous bowel movements (CSBM) continuous
timeFrame: Week 12
measure: Plasma zonulin
timeFrame: Week 12
Other outcomes:
Locations:
city: Waterloo
country: United States
facility: Cedar Valley Digestive Health Center
state: Iowa
Study officials:
affiliation: Cedar Valley Digestive Health Center
name: Richard A. Manfready, MD, AM, FACP
role: PRINCIPAL_INVESTIGATOR
affiliation: Cedar Valley Digestive Health Center
name: Ravindra Mallavarapu, MD
role: STUDY_CHAIR
affiliation: Cedar Valley Digestive Health Center
name: Harichandana Punukula, PharmD, MS
role: STUDY_DIRECTOR
References:
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.
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.
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.
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.
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.
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.
citation: 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.