Treatment with L-citrulline in patients with post-polio syndrome: study protocol for a single-center, randomised, placebo-controlled, double-blind trial

Simone Schmidt, Vanya Gocheva, Thomas Zumbrunn, Daniela Rubino-Nacht, Ulrike Bonati, Dirk Fischer, Patricia Hafner, Simone Schmidt, Vanya Gocheva, Thomas Zumbrunn, Daniela Rubino-Nacht, Ulrike Bonati, Dirk Fischer, Patricia Hafner

Abstract

Background: Post-polio syndrome (PPS) is a condition that affects polio survivors years after recovery from an initial acute infection by the Poliomyelitis virus. Most often, patients who suffered from polio start to experience gradual new weakening in muscles, a gradual decrease in the size of muscles (muscle atrophy) and fatigue years after the acute illness. L-citrulline is known to change muscular metabolism synthesis by raising nitric oxide (NO) levels and increasing protein synthesis. This investigator-initiated, randomised, placebo-controlled, double-blind, trial aims to demonstrate that L-citrulline positively influences muscle function and increases muscular energy production in patients with PPS.

Methods/design: Thirty ambulant PPS patients will be recruited in Switzerland. Patients will be randomly allocated to one of the two arms of the study (placebo:verum 1:1). After a 24-week run-in phase to observe natural disease history and progression, participants will be treated either with L-citrulline or placebo for 24 weeks. The primary endpoint is change in the 6-min Walking Distance Test. Secondary endpoints will include motor function measure, quantitative muscle force, quantitative muscle magnetic resonance imaging and magnetic resonance spectroscopy and serum biomarker laboratory analysis DISCUSSION: The aim of this phase IIa trial is to determine if treatment with L-citrulline shows a positive effect on clinical function and paraclinical biomarkers in PPS. If treatment with L-citrulline shows positive effects, this might represent a cost-efficient symptomatic therapy for PPS patients.

Trial registration: ClinicalTrial.gov, ID: NCT02801071 . Registered on 6 June 2016.

Keywords: Clinical trial; L-citrulline; Post-polio syndrome; Quantitative MRI.

Figures

Fig. 1
Fig. 1
Flow chart showing the study design
Fig. 2
Fig. 2
Planned visiting and examination schedule *will be used as baseline values. Vital signs include: blood pressure, heart rate, weight at every visit; height only at screening visit. Motor Function Measurement (MFM) scale, 6-min Walking Distance Test (6MWD), quantitative motor tests (QMT), and screening will be used as baseline values. Full blood count: erythrocytes, reticulocytes, leucocytes, platelets, haemoglobin, haematocrit. GOT, GPT, creatinine, electrolytes (Na+, K+, Ca2+), urea, creatine kinase (CK), glycosylated haemoglobin (HbA1c), cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, calculated glomerular filtration rate (GFR). Oxidised DNA (8-hydroxy-2’-deoxyguanosine: 8OHDG), carbonylated proteins (4-Hydroxynonenal (4-HNE)), mitochondrial proteins (citratsynthase, cytochrome C oxidase subunit 1, succinate dehydrogenase subunit A), nitrotyrosine, cGMP. Woman of child-bearing potential. SIPP – Self-reported Impairments in Persons with late effects of Polio, IBM-FRS – Inclusion Body Myositis Functional Rating Scale, WHOQOL-BREF – The WHO Quality of Life – BREF Questionnaire
Fig. 3
Fig. 3
Randomisation placebo:verum 1:1. Association of sample size (N) and the mean relative improvement of the verum group in the 6-min Walking Distance Test at follow-up (θ), assuming no improvement in the placebo group, for a randomisation ratio of 1:1 into the placebo and verum groups, respectively. Curves are smoothed for illustration purposes only

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