Tenapanor in Synucleinopathy-Related Constipation

NCT06460038 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2405-21279
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Synucleinopathy; Parkinson's Disease

Keywords

tenapanor; synucleinopathy; Parkinson's disease; constipation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Abdominal pain and bloating response

  6 of 12 weeks

• Calprotectin

  Week 12

• Lipopolysaccharide binding protein

  Week 12

• Complete spontaneous bowel movements (CSBM) continuous

  Week 12

• Plasma zonulin

  Week 12

Study Arms (2)

Tenapanor

EXPERIMENTAL

Tenapanor 50 mg orally twice daily for 12 weeks

Drug: Tenapanor

Placebo

PLACEBO COMPARATOR

Placebo orally twice daily for 12 weeks

Drug: Placebo

Interventions

Tenapanor DRUG

Inhibitor of NHE3

Tenapanor

Placebo DRUG

Placebo drug

Placebo

Eligibility Criteria

• Age: 50 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 50-89 years.
• Diagnosis of PD within Hoehn and Yahr stages 1-3, confirmed by a neurologist per International Parkinson and Movement Disorder Society criteria.
• 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.
• Stool consistency ≤3 on the Bristol Stool Form Scale (BSFS). This criterion will be verified during a 2-week screening period.
• Agreement to use contraception, if applicable.

You may not qualify if:

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

Sponsors & Collaborators

• Cedar Valley Digestive Health Center: lead
• Ardelyx: collaborator

Study Sites (1)

Cedar Valley Digestive Health Center

Waterloo, Iowa, 50701, United States

RECRUITING

Related Publications (7)

• 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.

  PMID: 34276285 BACKGROUND

• 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.

  PMID: 35633466 BACKGROUND

• 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.

  PMID: 37562457 BACKGROUND

• 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.

  PMID: 36801916 BACKGROUND

• 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.

  PMID: 28244495 BACKGROUND

• 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.

  PMID: 33337659 BACKGROUND

• 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.

  PMID: 31934897 BACKGROUND

MeSH Terms

Conditions

Synucleinopathies; Parkinson Disease; Constipation

Interventions

tenapanor

Condition Hierarchy (Ancestors)

Neurodegenerative Diseases; Nervous System Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Richard A. Manfready, MD, AM, FACP

  Cedar Valley Digestive Health Center

  PRINCIPAL INVESTIGATOR

• Ravindra Mallavarapu, MD

  Cedar Valley Digestive Health Center

  STUDY CHAIR

• Harichandana Punukula, PharmD, MS

  Cedar Valley Digestive Health Center

  STUDY DIRECTOR

Central Study Contacts

Richard A. Manfready, MD, AM, FACP

CONTACT

(319) 235-5390; rman@alum.mit.edu

Harichandana Punukula, PharmD, MS

CONTACT

319-888-8270; hpunukula@cvmspc.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind, placebo controlled trial of tenapanor vs. placebo

Study Record Dates

• First Submitted: June 11, 2024
• First Posted: June 14, 2024
• Study Start: January 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: February 10, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data requests can be submitted starting 6 months after article publication and the data will be made accessible for up to 24 months. Data will be available upon request for 2 years following study publication.
• Access Criteria: Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA).

Locations

US (1)