Clinical trial NCT02801071: L-Citrulline in Patients With Post-Polio Syndrome
Official title: "Treatment With L-citrulline in Patients With Post-polio Syndrome - a Randomized Double Blind Placebo Controlled Study"
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Post-Polio Syndrome
Keywords: Post-Polio Syndrome
PPS
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2016-06-15
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Mean change of 6 Minute Walking Distance(6MWD)
timeFrame: Baseline to week 48
Secondary outcomes:
measure: Mean change of motor function measure (MFM) total score
timeFrame: Baseline to week 48
measure: Change of quantitative muscle MRI (IDEAL-CPMG with T₂ and lipid quantitation and dynamic 31P-MR spectroscopy)
timeFrame: Baseline to week 48
measure: Change of serum concentrations for markers of muscle necrosis
timeFrame: Baseline to week 48
measure: Change of serum concentrations for markers of oxidative stress
timeFrame: Baseline to week 48
measure: Change of serum concentrations for markers of nitrosative stress
timeFrame: Baseline to week 48
measure: Change of serum concentrations for markers of mitochondrial related genes
timeFrame: Baseline to week 48
Other outcomes:
measure: Change of disease severity measured by questionnaires
timeFrame: Baseline to week 48
measure: Changes in Spinal cord MRI from week 48 to week 96
timeFrame: week 48 to week 96
measure: Changes in brain MRI from week 48 to week 96
timeFrame: week 48 to week 96
Locations:
city: Basel
country: Switzerland
facility: University of Basel, Children's Hospital
Study officials:
affiliation: University Children's Hospital Basel
name: Dirk Fischer, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.