Abstract OBJECTIVE: To analyse changes in muscle strength, physical performance and quality of life during intravenous immunoglobulin (IVIg) treatment in patients with post-polio syndrome.
DESIGN: Open clinical trial.Patients: A total of 14 patients (6 women, 8 men; mean age 57 years, range 43-67 years) were included in the study.
INTERVENTION: Treatment with 90 g IVIg (30 g daily for 3 days). Main outcome: Muscle strength, measured with dynamic dynamometry, muscle function, by means of performing the 6-minute walk test, and quality of life, analysed by means of the SF-36 questionnaire, were performed before and after treatment.
RESULTS: For quality of life there was a statistically significant improvement for all but one of the 8 multi-item scales of SF-36 when comparing data before and after treatment with IVIg. The multi-item scale most improved was Vitality. There was no significant increase in muscle strength and physical performance.
CONCLUSION: Data indicate that IVIg may have a clinically relevant effect, with an improvement in quality of life. The effect may be due to a decrease in an inflammatory process in the central nervous system, which earlier has been reported in patients with past-polio syndrome after IVIg treatment. Since a possible placebo effect cannot be ruled out, a randomized controlled study is needed. PMID: 16546773 [PubMed – indexed for MEDLINE] Eur J Neurol. 2007 Jan;14(1):60-5. Post-polio syndrome patients treated with intravenous immunoglobulin: a double-blinded randomized controlled pilot study. Farbu E, Rekand T, Vik-Mo E, Lygren H, Gilhus NE, Aarli JA. Department of Neurology, Haukeland University Hospital, Bergen, Norway. firstname.lastname@example.org Abstract Post-polio syndrome (PPS) is characterized by new muscle weakness, atrophy, fatigue and pain developing several years after the acute polio. Some studies suggest an ongoing inflammation in the spinal cord in these patients. From this perspective, intravenous immunoglobulin (IvIg) could be a therapeutic option. We performed a double-blinded randomized controlled pilot study with 20 patients to investigate the possible clinical effects of IvIg in PPS. Twenty patients were randomized to either IvIg 2 g/kg body weight or placebo. Primary endpoints were changes in pain, fatigue and muscle strength 3 months after treatment. Surrogate endpoints were changes in cerebrospinal fluid (CSF) cytokine levels. Secondary endpoints were pain, fatigue and isometric muscle strength after 6 months. Patients receiving IvIg reported a significant improvement in pain during the first 3 months, but no change was noted for subjective fatigue and muscle strength. CSF levels of tumour necrosis factor-alpha (TNF-alpha) were increased compared with patients with non-inflammatory neurological disorders. In conclusion, in this small pilot study no effect was seen with IvIg treatment on muscle strength and fatigue, however IvIg treated PPS patients reported significantly less pain 3 months after treatment. TNF-alpha was increased in the CSF from PPS patients. The results are promising, but not conclusive because of the low number of patients studied. PMID: 17222115 [PubMed –
indexed for MEDLINE] Xepol® (XP-28) The first medical treatment of Post-Polio Syndrome Xepol is the first pharmaceutical product to address the unmet medical need of patients suffering from Post-Polio Syndrome (PPS). Even though new infections from the poliovirus ceased in developed countries more than 30 years ago, many patients are now struggling with renewed complications from the disease. While rarely fatal, the neurological and muscular symptoms of PPS are lifelong and debilitating. There is no medical treatment besides physiotherapy and assistive devices. Approximately 30-40% of survivors of paralytic polio develop severe PPS. There are around 300,000 PPS patients in major Western markets. Product background The concept behind Xepol was first developed by Dr Henrik Gonzalez and Professor Kristian Borg, both scientists at the Karolinska Institute (Sweden), and is backed by strong evidence suggesting an underlying neuroinflammatory pathology. Xepol is an injectable biological product which is administered once every 9 – 12 months and down regulates the inflammatory process in the nervous system of PPS patients. It was acquired by Pharmalink as an original concept backed by preliminary positive clinical observations. Xepol is protected by patents in major markets. In addition, market exclusivity was achieved by a US Orphan Drug Designation granted in 2006. Given the prevalence of PPS, there is the potential to achieve orphan drug designation in all major markets. Development status Following positive preliminary clinical studies, Pharmalink sponsored a Phase III of Xepol in PPS. The trial clearly met one of its two primary endpoints, relating to muscle strength, and results were published in the Lancet. In a follow-on study trial, still double-blinded, a defined subset of patients met both original endpoints showing a reduction of inflammatory cytokines in the cerebrospinal fluid and a significant reduction of symptoms of PPS while also showing that Xepol is safe and well tolerated with few or no side-effects. Significant results were also shown in endpoints such as pain, walking ability and SF-36 scores. A confirmatory Phase III study will be a further step in the development of Xepol, creating a basis for regulatory applications in the US, Europe and other potential markets. Pharmalink has prepared plans for the Phase III trial to be conducted in the US. Pharmalink is actively seeking a partner to bring Xepol onto the market.Lancet Neurol. 2006 Jun;5(6):493-500. Intravenous immunoglobulin for post-polio syndrome: a randomised controlled trial. Gonzalez H, Sunnerhagen KS, Sjöberg I, Kaponides G, Olsson T, Borg K. Division of Rehabilitation Medicine, Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden. email@example.com Abstract BACKGROUND:
Survivors of poliomyelitis often develop increased or new symptoms decades after the acute infection, known as post-polio syndrome. Production of proinflammatory cytokines within the CNS indicates an underlying inflammatory process, accessible for immunomodulatory treatment. We did a multicentre, randomised, double-blind, placebo-controlled study of intravenous immunoglobulin in post-polio syndrome.
METHODS: 142 patients at four university clinics were randomly assigned infusion of either 90 g in total of intravenous immunoglobulin (n=73) or placebo (n=69) during 3 consecutive days, repeated after 3 months. Seven patients were withdrawn from the study. Thus, 135 patients were assessed per protocol. Primary endpoints were muscle strength in a selected study muscle and quality of life as measured with the SF-36 questionnaire (SF-36 PCS). Secondary endpoints were 6-minute walk test (6MWT), timed up and go (TUG), muscle strength in muscles not chosen as the study muscle, physical activity scale of the elderly (PASE), visual analogue scale (VAS) for pain, multidimensional fatigue inventory (MFI-20), balance, and sleep quality. Outcome tests were done immediately before the first infusion and 3 months after the second infusion. This study is registered with , number NCT00160082. FINDINGS: Compared with baseline, median muscle strength differed by 8.3% between patients receiving intravenous immunoglobulin and placebo, in favour of the treatment group (p=0.029). SF-36 PCS did not differ significantly between the groups after treatment (p=0.321). Differences in the subscale vitality score (p=0.042) and PASE (p=0.018) favoured the active treatment group. MFI-20, TUG, muscle strength in the muscles not chosen as the study muscle, 6MWT, balance, and sleep quality did not differ between groups. For the whole study population there was no significant change in pain, as determined by VAS. Nevertheless, patients who reported pain at the study start improved in the intervention group but not in the placebo group (p=0.037). Intravenous immunoglobulin was well tolerated.
INTERPRETATION: Intravenous immunoglobulin could be a supportive treatment option for subgroups of patients with post-polio syndrome. Further studies on responding subgroups, long-term effects, and dosing schedules are needed. PMID: 16713921 [PubMed – indexed for MEDLINE] Publication Types, MeSH Terms, Substances, Secondary Source ID LinkOut – more resourcesEfficacy and Safety of Xepol (Human Immunoglobulin) in Subjects With Post-Polio Syndrome (PPS) This study has been completed. First Received: September 9, 2005 Last Updated: April 2, 2007 History of Changes Sponsor: Pharmalink AB Information provided by: Pharmalink AB ClinicalTrials.gov Identifier: NCT00160082 Purpose The primary objective was to assess the effect of Xepol compared to placebo on physical health and on muscle strength in subjects with post-polio syndrome.The secondary objective was to assess the effect of Xepol compared to placebo on functional balance, activity patterns, pain, fatigue, sleep, vitality, muscular strength, pulmonary capacity, walking ability, balance and safety. Condition Intervention Post Polio Syndrome, PPS Drug: Xepol Study Type: Interventional Study Design: Allocation: Randomized Control: Placebo Control Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double-Blind Primary Purpose: Treatment Official Title: Efficacy and Safety of Xepol (Human Immunoglobulin) in Subjects With Post-Polio Syndrome (PPS): A Randomized, Two-Arm, Parallel, Double-Blind, Multi-Centre, Placebo Controlled Study Resource links provided by NLM: MedlinePlus related topics: Fatigue Polio and Post-Polio Syndrome Drug Information available for: Immunoglobulins Globulin, Immune U.S. FDA Resources Further study details as provided by Pharmalink AB: Primary Outcome Measures: Primary endpoints: Physical health was quantified using the SF-36 questionnaire scales summarized into the composite Physical Component Summary (PCS) measure. Muscular strength was measured using a dynamometer or anelectronic grip force sensor (GRIPPIT) depending on the musclechosen. Secondary Outcome Measures: Secondary endpoints: Functional balance was assessed by using the Timed “Up and Go” (TUG) test. Activity pattern was assessed by the Physical Activity Scale of the Elderly (PASE). Pain was assessed by a Visual Analogue Scale and by a pain drawing. Fatigue was assessed using the Multidimensional Fatigue Inventory (MFI-20) questionnaire. Vitality was assessed using the vitality subscale (VT) of SF-36 questionnaire. Sleep was assessed using the Sleep quality scale. Muscular strength measured by a dynamometer and an electronic grip force sensor (GRIPPIT) for those muscles not included as the primary endpoint. Walking ability was assessed by a 6 minutes walking test. Pulmonary capacity (vital capacity, FEV1, FEV %) was measured by a standard spirometer method. Balance was assessed as postural sway velocity and the subject’s ability to voluntarily sway to various locations in space (NeuroCom Balance Master) or balance assessed by static and dynamic posturography (Chattecx® balance system) Adverse events Vital signs (blood pressure and heart rate) Physical examination Laboratory tests Estimated Enrollment: 124 Study Start Date: January 2001 Estimated Study Completion Date: May 2003 Detailed Description: Study Rationale: In an earlier open and non-controlled study in 10 patients with PPS, Xepol was given during three days. The patients showed improvements in muscular strength and co-ordination and a decrease in pain. The aim of this study was to investigate if these findings can be confirmed in a larger, double-blind, randomised and placebo controlled study. There are no simple clinical findings and specific laboratory changes that can be used to indicate the severity and progress of PPS. Different self-reporting questionnaires and objective measures of disability have often been used in clinical studies including SF-36 questionnaire, muscle strength measurement and walking test. The primary and secondary variables in this study were based on the clinical experience and literature reviewed. Eligibility Ages Eligible for Study: 18 Years to 75 Years Accepts Healthy Volunteers: No Criteria Inclusion Criteria: Male or female subjects ≥18 to ≤75 years of age. Post-polio syndrome according to Halstead and Gawne: History of polio virus infection Restitution or improvement regarding motor function and disabilities after initial infection Confirmed polio by EMG Subjectively increased muscular weakness after a period of at least 15 years functional stability No other explanation but post-polio syndrome to the symptoms Confirmed polio by EMG in the lower extremities in at least two of the following major muscle groups; musculi quadriceps, gastrocnemicus and tibialis anterior. (Two affected muscle groups in the same extremity were accepted). Subjectively increased muscular difficulties or pain after a period of at least 15 years functional stability. A muscle that had deteriorated within the last five years, and had 20-75 % of the muscle strength compared to age matched normal population when measured by a dynamometer or an electronic grip force sensor (GRIPPIT). Stable weight (defined as weight change 10 mkat/l. Any disease or treatment that according to the discretion of the Investigator could pose a medical threat to the subject in combination with study drug, i.e. clinical manifested severe cardiovascular disease or severe arteriosclerosis or severe psychiatric disorder or other treatment that affected the immunological system such as prednisone and methotrexate. Any disease or condition that according to the discretion of the Investigator would obstruct the subject from performing the tests in the protocol (e.g. fill in the questionnaires). Conditions associated with a risk of poor protocol compliance (e.g. known drug or alcohol abuse). Previous participation in the study. Contacts and Locations Please refer to this study by its ClinicalTrials.gov identifier: NCT00160082 Locations Sweden Danderyd Hospital Danderyd, Sweden Sahlgrenska University Hospital Gothenburg, Sweden Huddinge University Hospital Stockholm, Sweden, SE-141 86 Uppsala Academic Hospital Uppsala, Sweden Sponsors and Collaborators Pharmalink AB Investigators Principal Investigator: Kristian Borg, MD, Prof Department of Rehabilitation Medicine;Huddinge University Hospital; Stockholm, Sweden More Information Inmunoterapias y vacunas para los no tradicionales Indicaciones Informe.
Resumen OBJETIVO: Analizar los cambios en la fuerza muscular, el rendimientofísico y la calidad de vida durante la inmunoglobulina intravenosa (IgIV) en pacientescon síndrome post-polio.
DISEÑO: trial.Patients Abrir clínicos: Un total de 14 pacientes (6 mujeres, 8 hombres, con una edad media de 57 años, rango 43-67 años) fueron incluidos en el estudio.
INTERVENCIÓN: El tratamiento con IgIV 90 g (30 g al día durante 3 días).Desenlaces principales: La fuerza muscular, medida con dinamometría dinámica, la función muscular, mediante la realización de la prueba de caminata de 6 minutos, y la calidad de vida, analizados por medio del cuestionario SF-36, se realizaron antesy después del tratamiento.
RESULTADOS: Por la calidad de vida hubo una mejoría estadísticamentesignificativa para todos, pero una de las 8 escalas multi-ítem del cuestionario SF-36cuando se comparan los datos antes y después del tratamiento con IgIV. La escalamulti-ítem que más ha mejorado es la vitalidad. No hubo aumento significativo en la fuerza muscular y el rendimiento físico.