Home | NeuroEPO in patients with Parkinson disease stage II-III
11 June 2018 - 2:53pm by CIM3 June 2024 - 2:19pm by CIM
Changes to Authorization date
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2018-06-09 04:00:00
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2018-06-09 00:00:00
Changes to Clinical sites
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Not applicable
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Havana, National Institute of Neurology, MD. Alexis Soto Lavastida, Second degree specialist in Neurology
Changes to Recruitment status
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Recruiting
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Complete
Changes to Data sharing plan
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No
Changes to Date of first enrollment
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2017-12-08 05:00:00
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2017-12-08 00:00:00
Changes to Final enrolment number
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102
Changes to Study completion date
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2021-04-06T00:00:00
Changes to Date of available results
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2023-07-31T00:00:00
Changes to Record Verification Date
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2017/02/01
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2024/06/03
Changes to Next update date
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2018/02/01
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2025/06/03
Changes to Source(s) of monetary or material support
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Center of Molecular Immunology (CIM)
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Center of Molecular Immunology (CIM)Ministry of Public Health (MINSAP)
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Ministry of Public Health (MINSAP)
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Changes to Summary study
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EFFICIENCY RESULTS
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The study hypothesis predicted a neurological recovery, expecting the decrease in the UPDRS-MDS to be at least 3 points lower than the control group. This hypothesis was not fulfilled, even when there was improvement (decrease in the total UPDRS-MDS score in all groups). These started from a UPDRS-MDS median that ranged in each group from 67, 71 and 72 points for NeuroEPO 0.5, 1.0 and placebo, respectively, with a p-value of 0.809. At 6 months no significant differences were detected between the groups; the median of UPDRS-MDS in this evaluation is reported by group of 43, 44 and 47 points respectively, with a p-value of 0.772. At 9 months in the groups treated with neuroEPO no statistically significant changes were detected showing the following median values ​​48, 45 and 48 points respectively and a p-value of 0.820. Comparing initial values ​​- 6 months there are no significant differences between the groups treated with neuroEPO and the Placebo group. At 9 months the trend continues towards a decrease in the values ​​of the scale, with median values ​​of 23, 20 and 21 points respectively and a p-value of 0.993. The magnitude of the observed differences was 0.0 and 0.4 points (UPDRS-MDS value) in the 0.5 mg and 1.0 mg groups vs. placebo, respectively.
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It is considered that the main cause, despite the fact that the group treated with neuroEPO achieved the improvement in the UPDRS-MDS score, does not show significant differences vs. the placebo group, is attributed to the Placebo Effect. The neuroEPO molecule is proposed as a neuroprotector, not as an antiparkinsonian drug, with which the placebo effect may even exceed its symptomatic effect in patients with PD, as was demonstrated in this study. All actions that induce the expectation of benefit can act like a placebo, positively impacting the brain circuits in these patients. Placebo-associated improvement in PD has been found to be independent of gender, age, disease duration, and baseline disability score as measured by the UPDRS-MDS. The challenges in studying the placebo effect in clinical trials is the use of biomarkers to predict it.
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With respect to Neuropsychology, the analysis carried out using the measures of central tendency (mean, median, standard deviation, and percentages by categories) for the comparison between the three groups in time; 0 and 9 months, as well as the final-initial difference in each group, A and B with respect to the control group C, did not show significant differences. All the patients improved.
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In the Connectivity analysis, the three groups showed a decrease in global synchronization for the alpha frequency band and an increase in theta frequency with different topography. Group A (0.5mg) showed a very slight increase in synchronization for the beta and theta frequency bands, the latter located towards the frontal and central regions of the right hemisphere. Group B (1.0mg) showed similar results to group A, noting a slight increase in synchronization in addition to the delta frequency and in group C (placebo) the marked increase in synchronization stands out for the theta frequency band, which unlike group A showed a global topography, and a decrease for the beta, alpha and delta frequencies in the patients after having received the treatment (permutation test p<0.05 for all cases). Functional connectivity by EEG demonstrated the structuring of the functional network in groups A and B after treatment, which evidenced a change in the organization dependent on the delta band. This result could suggest the changes in the brain networks in groups A and B. The modifications found in group C point to a disruption of the functional network in terms of segregation and integration that involves the delta, theta and alpha bands. Functional connectivity translates changes in functional brain networks without defining improvement or worsening. It needs to be integrated into clinical outcomes.
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Despite not fulfilling the hypothesis raised from the clinical point of view, in practice total permanence in the protocol of the research subjects was observed, as well as motor changes in gait, the ability to go up and down the stairs in the place research, increased independence, the family commented on the participation of patients in home tasks and activities. It was always striking that some improved more than others and that the parameters evolved differently in each patient. Non-motor symptoms also improved since in this disease there are multiple complaints from the mourners and in the group that constituted the study sample it was found that complaints due to insomnia and constipation disappeared, these changes were the most frequent in general. . Faced with this evidence, it was decided to carry out other evaluations with the Univariate analysis and the Causality analysis that demonstrated motor and non-motor results in the study groups with significant differences in relation to the placebo group.
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SAFETY RESULTS
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Intranasally administered neuroEPO is safe for patients with Hoehn and Yahr stage II III Parkinson's disease, the safety analysis in the study showed that neuroEPO treatment was well tolerated and safe. Twenty-six AEs were recorded, those classified as mild predominated, with an unrelated causal relationship and did not lead to changes in treatment. The most frequent AEs were: nasal stinging sensation, hyperuricemia, decreased hemoglobin and hematocrit. The AE nasal burning in one patient was considered related to the use of the study drug and occurred in the neuroEPO 1 mg group.
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CONCLUSIONS
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- NeuroEPO shows no evidence of efficacy in patients with Hoehn and Yahr stage II-III Parkinson's disease as measured by total UPDRS-MDS. The final median in the UPDRS-MDS evaluation in both PP and ITT and in the three treatment groups decreased with respect to the initial evaluation, thus decreasing the values ​​over time, but did not show statistically significant differences in the comparison between groups.
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- The neuroEPO molecule is proposed as a neuroprotective agent, not as an antiparkinsonian drug, with which the placebo effect may even exceed its symptomatic effect in patients with PD.
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The univariate and causal analysis shows efficacy in the motor and cognitive variables in the sample of patients with Hoehn and Yahr stage II III Parkinson's disease.
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- NeuroEPO is safe in patients with Hoehn and Yahr stage II III Parkinson's disease, taking into account that the adverse events related to the product were mild, reversible and did not compromise the lives of the patients.
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- Motor, cognitive and affective parameters in PD patients treated with neuroEPO and with placebo all improved in all three treatment groups.
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- Functional connectivity by EEG shows a structuring of the functional network in groups A and B while in group C they point to a breakdown of the functional network.
Revision of 3 June 2024 - 2:19pm: