Clinical trial NCT04110678: Tolerance to NeuroEPO in Parkinson Disease
Official title: Nasal Administration of the NeuroEPO in Parkinson Disease: Short-term Tolerance Physician Lead Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Parkinson Disease
Keywords: Parkinson Disease
Tolerance
NeuroEPO
side effects
UPDRS
Cognition
Lead sponsor: International Center for Neurological Restoration, Cuba
Sponsor class: OTHER
Collaborators: name: Center of Molecular Immunology, Cuba
name: University of Electronic Science and Technology of China
First posted: 2019-10-01
Enrollment: 26
Sex: ALL
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, blinded, Physician lead trial
Primary purpose: TREATMENT

Brief summary: Treatment strategies in Parkinson's disease (PD) can improve a patient's quality of life but cannot stop the progression of PD. The investigators are looking for different alternatives that modify the natural course of the disease and recent research has demonstrated the neuroprotective properties of erythropoietin. In Cuba, the Center for Molecular Immunology (CIM) is a cutting edge scientific center where the recombinant form (EPOrh) and recombinant human erythropoietin with low sialic acid (NeuroEPO) are produced.

Detailed description: Delivery of therapeutic agents as erythropoietin (EPO) into Central Nervous System through intranasal route could benefit patients with neurological disorders. A new nasal formulation containing a non-hematopoietic recombinant EPO (NeuroEPO) has shown neuroprotective actions in preclinical models and the safety trial of NeuroEPO was evaluated for the first time in humans in Cuba.

The researchers previously conducted a proof of concept clinical trial, administering EPOrh subcutaneously where the neuropsychological performance was measured as a secondary endpoint. This protocol has the register number NCT01010802. Results showed an increased neuropsychological performance of patients after administration as compared to before administration results.

In this protocol two institutions were leading a physician clinical trial.The two institutions: International Center for Neurological Restoration (CIREN from Centro Internacional de Restauracion Neurologica from Spanish) where the recruitment and clinical evaluation of the PD patients will be done and the Center for Molecular Immunology, who was the promoter.

Randomisation will be performed by the CIM to assign the patients to groups. The groups will receive neuroEPO or placebo with identical organoleptic characteristics. The informed consent of all patients will be obtained before the start of the trial after the selection and primary evaluation of the inclusion criteria.

The dose of neuroEPO will be a vial with a dose of 1 mL/1mg administered intra-nasally for five consecutive weeks. The placebo group was administered 1 mL of an intranasal inert solution for the same period of time.

The IBM SPSS Statistics V 21 package will be used for the statistical analysis of the data. The investigators will use tables of frequency analysis and descriptive statistics to analyse the demographic characteristics of the sample.

The analysis of the results obtained will be done studying the differences between quantitative variables for paired and unpaired samples, the Wilcoxon and U of Mann-Whitney tests will be used respectively. For the qualitative variables Chi square (X2) test will be used. All values of p \< 0.05 will be considered significant.

Eligibility criteria: Inclusion Criteria:

* Patient who fulfilled the London Brain Bank's operational criteria for PD
* Willing to participate in the study;
* ≥1 year since disease onset;
* Good response to antiparkinsonian treatment with levodopa (\>30% change in motor score on the motor section of the Unified Parkinson's Disease
* no prior poly globulin (hematocrit ≤50%);

Exclusion Criteria:

* Refusal to participate;
* Known hypersensitivity to products derived from eukaryotes or hypersensitivity to human albumin;
* Pregnancy or breastfeeding;
* Hypertension;
* Immunosuppressant, androgen or anabolic steroid treatment in the month prior to recruitment;
* Sepsis or active infection;
* Active acute or chronic inflammatory diseases;
* Haematological diseases, such as sickle cell disease, myelodysplastic syndromes, active clotting or bleeding disorders;
* Malignant tumor or cancer treatment;
* Alcoholism or drug addiction in the two years prior to inclusion assessment.
* Significant cognitive decline as measured by clinical assessment, DRS (Dementia Rating Scale) and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV).

Primary outcomes:
measure: Number of participants with local nasal events
timeFrame: day 1-5
measure: Number or participants with increment in the haematological and biochemistry parameters
timeFrame: day 0 day 5 and day 14
measure: Change from Baseline Systolic Blood Pressure after each intervention
timeFrame: day 1-5
Secondary outcomes:
Other outcomes:
Locations:
city: Havana
country: Cuba
facility: Clinic of Movement Disorders, International Center for Neurological Restoration
city: La Habana
country: Cuba
facility: Centro Inmunologia Molecular CIM
Study officials:
affiliation: Centro Inmunologia Molecular CIM Havana Cuba
name: Daniel E Amaro Gonzalez, PhD Eng
role: PRINCIPAL_INVESTIGATOR
affiliation: Centro Immunologia Molecular CIM Havana Cuba
name: Teresita Rodríguez Obaya, PhD
role: STUDY_CHAIR
affiliation: Centro Nacional Producción Animales de Laboratorio (CENPALAB) Cuba
name: Iliana Sosa Teste, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pedroso I, Garcia M, Casabona E, Morales L, Bringas ML, Perez L, Rodriguez T, Sosa I, Ricardo Y, Padron A, Amaro D. Protective Activity of Erythropoyetine in the Cognition of Patients with Parkinson's Disease. Behav Sci (Basel). 2018 May 21;8(5):51. doi: 10.3390/bs8050051. eCollection 2018 May.
citation: Bringas Vega ML, Pedroso Ibanez I, Razzaq FA, Zhang M, Morales Chacon L, Ren P, Galan Garcia L, Gan P, Virues Alba T, Lopez Naranjo C, Jahanshahi M, Bosch-Bayard J, Valdes-Sosa PA. The Effect of Neuroepo on Cognition in Parkinson's Disease Patients Is Mediated by Electroencephalogram Source Activity. Front Neurosci. 2022 Jun 30;16:841428. doi: 10.3389/fnins.2022.841428. eCollection 2022.
citation: Garcia-Llano M, Pedroso-Ibanez I, Morales-Chacon L, Rodriguez-Obaya T, Perez-Ruiz L, Sosa-Teste I, Amaro-Gonzalez D, Bringas-Vega ML. Short-term Tolerance of Nasally-administered NeuroEPO in Patients with Parkinson Disease. MEDICC Rev. 2021 Jan;23(1):49-54. doi: 10.37757/MR2021.V23.N1.10. Epub 2021 Jan 30.