L-Citrulline in Patients With Post-Polio Syndrome

"Treatment With L-citrulline in Patients With Post-polio Syndrome - a Randomized Double Blind Placebo Controlled Study"

The purpose of the study is to show that the intake of L-citrulline improves muscle function in patients with Post-Polio Syndrome (PPS).

Study Overview

• Status: Completed
• Conditions: Post-Polio Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: 15g L-citrulline daily p.o.

Detailed Description

This is a single center, randomized, double-blind, placebo controlled study. The study medication consists of L-citrulline, respectively placebo given orally; 5 g L-citrulline or placebo will be given three times daily. The duration of the study is 48 weeks and comprehends one screening and four study visits.

Additionally, in order to investigate whether PPS is associated with an atrophy of spinal cord gray and potentially also white matter as well as motor cortex atrophy, it is planned to offer all trial participants an additional optional spinal cord/brain MRI investigation and a MRI at week 48 and a follow-up one year later together with a clinical and physiotherapy assessment during extension phase. We don't expect Citrulline to affect the spinal cord gray or white and gray matter.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 3

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4056
    • University of Basel, Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Prior paralytic poliomyelitis with evidence of motor neuron loss
• A period of partial or complete functional recovery after acute paralytic Poliomyelitis
• Slowly progressive and persistent new muscle weakness or decreased endurance, with or without generalized fatigue, muscle atrophy, or muscle and joint pain. Symptoms that persist for at least a year
• Exclusion of other neuromuscular, medical and skeletal abnormalities as causes of symptoms
• Patients older than 18 years at time of Screening
• ambulant
• ability to walk 150m in the 6 min. Walking distance (6MWD)
• females of childbearing potential willing to use contraceptive during the study

Exclusion Criteria:

• Previous (3 months or less) or concomitant participation in any other therapeutic trial
• Use of L-citrulline or L-arginine within the last 3 months
• Known individual hypersensitivity to L-citrulline
• Known or suspected malignancy
• Other chronic disease or clinical relevant limitation of renal, liver, heart function according to discretion of investigator
• Pregnant or breast-feeding women
• Severe renal failure (calculated glomerular filtration rate (GFR) < 30 ml/min)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: L-citrulline; 15 g L-citrulline p.o. per day (3x 5g) for 24 weeks	Drug: 15g L-citrulline daily p.o.
Placebo Comparator: Placebo; L-citrulline Placebo 3 times daily p.o. for 24 weeks	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean change of 6 Minute Walking Distance(6MWD)	Baseline to week 48

Secondary Outcome Measures

Outcome Measure	Time Frame
Mean change of motor function measure (MFM) total score	Baseline to week 48
Change of quantitative muscle MRI (IDEAL-CPMG with T₂ and lipid quantitation and dynamic 31P-MR spectroscopy)	Baseline to week 48
Change of serum concentrations for markers of muscle necrosis	Baseline to week 48
Change of serum concentrations for markers of oxidative stress	Baseline to week 48
Change of serum concentrations for markers of nitrosative stress	Baseline to week 48
Change of serum concentrations for markers of mitochondrial related genes	Baseline to week 48

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of disease severity measured by questionnaires	Mean change of disease severity as assessed by a combination of the Self-Reported Impairments in Persons With Late Effects of Polio Rating Scale (SIPP-RS), the Inclusion Body Myositis Functional Rating Scale (IBM-FRS) and the World Health Organization Quality Of Life (WHOQOL-BREF)	Baseline to week 48
Changes in Spinal cord MRI from week 48 to week 96	Determination of the degree of spinal cord gray and white matter atrophy in PPS patients in comparison to healthy controls and its relationship to physical disability (QMT).; Determination of the degree of motor cortex atrophy in PPS patients compared to healthy controls and its association with spinal cord gray and white matter atrophy in PPS patients.; Determination of the association between spinal cord gray matter atrophy and microstructural alterations as assessed by diffusion tensor imaging.; Test the suitability of the applied, optimized imaging and post-processing methods for longitudinal data.	week 48 to week 96
Changes in brain MRI from week 48 to week 96	Determination of the degree of spinal cord gray and white matter atrophy in PPS patients in comparison to healthy controls and its relationship to physical disability (QMT).; Determination of the degree of motor cortex atrophy in PPS patients compared to healthy controls and its association with spinal cord gray and white matter atrophy in PPS patients.; Determination of the association between spinal cord gray matter atrophy and microstructural alterations as assessed by diffusion tensor imaging.; Test the suitability of the applied, optimized imaging and post-processing methods for longitudinal data.	week 48 to week 96

Collaborators and Investigators

• Sponsor: Dirk Fischer
• Investigators: Principal Investigator: Dirk Fischer, Prof., University Children's Hospital Basel

Publications and helpful links

General Publications

• Gocheva V, Hafner P, Orsini AL, Schmidt S, Schaedelin S, Rueedi N, Rubino-Nacht D, Weber P, Fischer D. Health-related quality of life, self-reported impairments and activities of daily living in relation to muscle function in post-polio syndrome. J Patient Rep Outcomes. 2020 Jul 16;4(1):59. doi: 10.1186/s41687-020-00226-5.
• Schmidt S, Gocheva V, Zumbrunn T, Rubino-Nacht D, Bonati U, Fischer D, Hafner P. Treatment with L-citrulline in patients with post-polio syndrome: study protocol for a single-center, randomised, placebo-controlled, double-blind trial. Trials. 2017 Mar 9;18(1):116. doi: 10.1186/s13063-017-1829-3.

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2016
• Primary Completion (Actual): August 15, 2017
• Study Completion (Actual): October 5, 2018

Study Registration Dates

• First Submitted: June 6, 2016
• First Submitted That Met QC Criteria: June 10, 2016
• First Posted (Estimate): June 15, 2016

Study Record Updates

• Last Update Posted (Actual): January 23, 2019
• Last Update Submitted That Met QC Criteria: January 21, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Post-Polio Syndrome; PPS
• Additional Relevant MeSH Terms: Pathologic Processes; Central Nervous System Diseases; Nervous System Diseases; RNA Virus Infections; Virus Diseases; Infections; Disease; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Central Nervous System Infections; Neurodegenerative Diseases; Enterovirus Infections; Picornaviridae Infections; Spinal Cord Diseases; Muscular Disorders, Atrophic; Myelitis; Syndrome; Poliomyelitis; Postpoliomyelitis Syndrome
• Other Study ID Numbers: PPS

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No