Revisions for NeuroEPO in mild-moderate Alzheimer's disease | Registro Público Cubano de Ensayos Clínicos

--- 20 September 2022 - 3:43pm by Gladys
+++ 4 June 2024 - 11:02am by CIM
+-01-19 00:00:00
-In process
+/05.008.22BA
 Havana,  Hermanos Ameijeiras(HHA) (principal site) Hospital,  PhD. Nelson Gómez Viera, second degree specialist in neurology
 Havana, Dr. Carlos J. Finlay Hospital, Ariadna Martinez Chile Ph.D , first degree specialist in neurology
-Havana, Manuel Fajardo Hospital, Emilio Manuel Zayas Somoza Ph.D, first degree specialist in Geriatrics-Gerontology
 Havana, Salvador Allende Hospital, Jorge Luis Matos Ph.D, first degree specialist in neurology
 Havana, Enrique Cabrera Hospital, Sunaidy Valdez Busques Ph.D , first degree specialist in neurology
 Havana, Medical and Surgical Research Center  (CIMEQ), Hermys Treto Vega Ph.D ,  first degree specialist in neurology
-Havana, The Ibero-American Center for the Elderly (CITED), Damian Gilberto Varona Gutierrez Ph.D, first degree specialist in Geriatrics-Gerontology
 Havana, International Center of Neurological Restoration  (CIREN), Yordanka M. Ricardo de la Fe Ph.D, first degree specialist in neurology
 Havana, Cuban Neurosciences Center (CNEURO), Evelio Gonzalez Dalmau Ph.D, Degree in physics
 Havana, Cristobal Labra Polyclinic,  Ana Lidia Rodriguez Blanco Ph.D, second degree Specialist in Internal Medicine and Comprehensive General Medicine
 Havana, Center for Clinical Research of Isotopes Center, Yamile Peña Quian Ph.D, second degree specialist in Internal Medicine (nuclear doctor).
-Pending
+Recruiting
--10-15 00:00:00
+-03-20 00:00:00
 Group A - neuroEPO (Experimental): 0.5 mg dose of neuroEPO (equivalent to 0.5 mL), 0.25 mL nasal drops in each nostril, 3 times a week (Monday, Wednesday and Friday), for 78 weeks.
-Group B - Donepezilo (Control): Donepezil (5.0 mg) (oral tablets) daily for one month (4 weeks) and then the same dose can be maintained or increased to 10 mg (according to the patient's response) for 78 weeks.
+Group B - Donepezilo (Control): Donepezil (10 mg) (oral tablets) daily for 78 weeks.
-Group C – neuroEPO+Donepezilo (Experimetal): Combination of neuroEPO 0.5 mg (0.5 mL) nasal drops 0.25 mL in each nostril, 3 times a week (Monday, Wednesday and Friday) and Donepezil (5.0 mg) (oral tablets) daily for one month (4 weeks) and then the same dose can be maintained or increased to 10 mg (according to the patient's response). Both treatments for 78 weeks.
+Group C – neuroEPO+Donepezilo (Experimetal): Combination of neuroEPO 0.5 mg (0.5 mL) nasal drops 0.25 mL in each nostril, 3 times a week (Monday, Wednesday and Friday) and Donepezil (10 mg) (oral tablets) daily for, both treatments are for 78 weeks.
 years
 . Patients and/or caregivers who give their consent to participate in the study by signing the informed consent form.
 . Patient with a caregiver physically and mentally able to understand the study and willing to collaborate with the research.
-. Patients aged ≥ 19 years.
+. Patients aged ≥ 50 years.
-. Patients with GDS from 3 to 5 points.
+. Patients with GDS from 3 to 5 points, inclusive.
-. Patients with a CDR of 1 to 2 points.
+. Patients with a CDR of 1 to 2 points, inclusive.
-. ADAScog11 score from 16 to 30 points.
+. ADAScog11 score from 16 to 30 points, inclusive.
 . Patients with patent airways.
-. Medical condition (not Alzheimer's disease) that may be contributing to cognitive impairment in the subject (substance abuse, AIDS, syphilis, stroke or other cerebrovascular disease, head trauma, brain tumor).
+. Medical condition (not Alzheimer's disease) that may be contributing to cognitive impairment in the subject (substance abuse, AIDS, syphilis, stroke or other cerebrovascular disease, head trauma, brain tumor, psychiatric illness).
-. Unstable/uncontrolled psychiatric illness (example: major depression, schizophrenia, bipolar disorder).
+. History of unstable angina, acute myocardial infarction, cancer, Parkinson's disease, coagulation disorders, anemia, and chronic/decompensated liver or kidney disorders.
-. History of unstable angina, acute myocardial infarction, cancer, Parkinson's, kidney disease, liver disease, coagulation disorders, anemia.
+. Any contraindication that does not allow MRI, SPECT-CT or PET-CT to be performed.
-. Any contraindication that does not allow the performance of MRI, SPECT or PET.
+. Subjects receiving treatment with antipsychotics, barbiturates, monoamine oxidase inhibitors, benzodiazepines and antidepressants, at doses that may compromise neuropsychological tests.
-. Subjects receiving treatment with antipsychotics, barbiturates, monoamine oxidase inhibitors, benzodiazepines and antidepressants, at doses that may compromise neuropsychological tests.
+. Patients who are receiving any of the medications approved for Alzheimer's disease (donepezil, rivastigmine, galantamine, memantine, aducanumab, NeuralCIM)
-. Patients receiving any of the approved medications for Alzheimer's disease (donepezil, rivastigmine, galantamine, memantine, aducanumab, neuroEPO)
+. Patients with a history of hypersensitivity to hr-EPO or any component of the product.
-. Patients with a history of hypersensitivity to hr-EPO or any component of the product.
+. Patients with known sensitivity to Donepezil hydrochloride, piperidine derivatives or some of the excipients used in the formulation.
-. Patients with known sensitivity to donepezil hydrochloride, piperidine derivatives or any of the excipients used in the formulation.
+. Alcoholism.
-. Patients with nasal irritation (sneezing) or runny nose before starting treatment.
+. Patients receiving treatment with anticoagulants.
-. Alcoholism.
-Pharmacy degree
+Pharmacy degree, PhD
-/09/20
+/06/04
-/09/20
+/06/04

NeuroEPO in mild-moderate Alzheimer's disease

General information

Section to complete general information about the trial: scientific and public title, protocol identifiers, sponsors and Source(s) of Monetary or Material Support.

Scientific title:

Evaluation of the efficacy and safety of the administration of neuroEPO/neuroEPO-donepezil vs. donepezil in patients with mild-moderate Alzheimer's disease.

Secondary indentifying numbers:

Not applicable

Issuing authority of the secondary identifying numbers:

Not applicable

Source(s) of monetary or material support:

Center of Molecular Immunology (CIM), Ministry of Public Health (MINSAP)

Authorization for beginning

Section to complete information about the regulatory approval of clinical trial: regulatory agency name, approval date and reference number in the agency.

Regulatory instance to authorize the initiation of the study:

Center for State Control of Drugs, Medical Devices and Equipment (CECMED)

Authorization date :

19/01/2023

Reference number:

17/05.008.22BA

Principal investigator

Section to complete information about Email address, telephone number and postal address of the Principal Investigator.

First name:

Giosmany

Last name:

Bringas Sanchez

Medical Specialty :

First Degree Specialist in Neurology

Affiliation:

Institute of Neurology and Neurosurgery (INN)

Postal address:

Calle D y 29. Vedado. Plaza

City:

Havana

Country:

Cuba

Zip Code:

10400

Telephone:

+53-78345504

Email address:

giosmany.bringas@inn.sld.cu

Clinical sites to participate

Section to complete the data related to the clinical sites involved in the trial: site and responsible investigator for every site.

Countries of recruitment:

Cuba

Clinical sites:

Havana, Hermanos Ameijeiras(HHA) (principal site) Hospital, PhD. Nelson Gómez Viera, second degree specialist in neurology

Havana, Dr. Carlos J. Finlay Hospital, Ariadna Martinez Chile Ph.D , first degree specialist in neurology

Havana, Salvador Allende Hospital, Jorge Luis Matos Ph.D, first degree specialist in neurology

Havana, Enrique Cabrera Hospital, Sunaidy Valdez Busques Ph.D , first degree specialist in neurology

Havana, Medical and Surgical Research Center (CIMEQ), Hermys Treto Vega Ph.D , first degree specialist in neurology

Havana, International Center of Neurological Restoration (CIREN), Yordanka M. Ricardo de la Fe Ph.D, first degree specialist in neurology

Havana, Cuban Neurosciences Center (CNEURO), Evelio Gonzalez Dalmau Ph.D, Degree in physics

Havana, Cristobal Labra Polyclinic, Ana Lidia Rodriguez Blanco Ph.D, second degree Specialist in Internal Medicine and Comprehensive General Medicine

Havana, Center for Clinical Research of Isotopes Center, Yamile Peña Quian Ph.D, second degree specialist in Internal Medicine (nuclear doctor).

Recruitment status

Section to complete information about the recruitment status and the date of first enrolment subject

Recruitment status:

Recruiting

Date of first enrollment:

20/03/2023

Health condition and Intervention

Section to complete information about the primary medical condition(s) or problem(s) studied and, a characteristics of the intervention(s).

Health condition(s) or Problem(s) studied:

mild-moderate Alzheimer's disease

Health condition(s) code:

Alzheimer Disease

Dementia

Brain Diseases

Central Nervous System Diseases

Nervous System Diseases

Tauopathies

Neurodegenerative Diseases

Neurocognitive Disorders

Mental Disorders

Intervention(s):

Group A - neuroEPO (Experimental): 0.5 mg dose of neuroEPO (equivalent to 0.5 mL), 0.25 mL nasal drops in each nostril, 3 times a week (Monday, Wednesday and Friday), for 78 weeks. Group B - Donepezilo (Control): Donepezil (10 mg) (oral tablets) daily for 78 weeks. Group C – neuroEPO+Donepezilo (Experimetal): Combination of neuroEPO 0.5 mg (0.5 mL) nasal drops 0.25 mL in each nostril, 3 times a week (Monday, Wednesday and Friday) and Donepezil (10 mg) (oral tablets) daily for, both treatments are for 78 weeks.

Intervention code:

Erythropoietin

Neuroprotective Agents

Donepezil

Tablets

Administration, Intranasal

Administration, Oral

Intervention keyword:

NeuroEPO nasal drops

Outcomes and Timepoint

Section to complete information about primary and secondary outcomes including. It includes the metric or method of measurement used and, the time point for every outcome.

Primary outcome(s):

ADAScog11 (10-15 points: mild cognitive impairment. 16-24 points: mild stage. 25-30 points: moderate stage. 31-45 points: moderate-severe stage. > 45 points : severe stage). Measurement time: Baseline (before starting treatment), weeks 52 and 78.

Key secondary outcomes:

Efficacy related: 1. Degree of dementia. Measured by GDS (1 Absence of cognitive deficit. 2 Very mild cognitive deficit, 3 Mild cognitive deficit, 4 Moderate cognitive deficit, 5 Moderately severe cognitive deficit, 6 Severe cognitive deficit, 7 Very severe cognitive deficit. Measurement time: start, weeks 52 and 78. 2. Classification of dementia by CDR (0: No deterioration.0.5: Doubtful deterioration.1: Mild deterioration.2: Moderate deterioration. 3: Severe deterioration.). Measurement time: start, weeks 52 and 78. 3. General cognitive status. Measured by MoCA (≥ 26 points: Normal, 25-22 points: MCI, 21-18 points: mild impairment, 17-14 points: moderate impairment, < 14 points: severe impairment. Measurement time: start, weeks 52 and 78. 4. Global assessment of the patient's condition. Measured by CIBIC plus (1 point: Marked improvement. 2 points: Moderate improvement. 3 points: Minimal improvement. 4 points: No change. 5 points: Minimal worsening. 6 points: Moderate worsening. 7 points: Marked worsening. Measurement time: weeks 52 and 78. 5. Validity index in the basic activities of daily life. Measured by Katz Index (A. Independent in all functions B. Independent in all functions except any one, C. Independent in all functions except in the bathroom and any other, D. Independent in all functions except in the bathing, dressing and any other, E. Independent in all functions except bathing, dressing, toileting and any other, F. Independent in all functions except bathing, dressing, toileting, mobility and any other , G. Dependent on all functions, H. Dependent on at least two functions, but not classifiable as C, D, E or F) . Measurement time: start, weeks 52 and 78. 6. Validity index in instrumental activities of daily living. Measured by Lawton Index (Female: 0-1 point Total Dependence, 2-3 points Severe, 4-5 points Moderate, 6-7 points mild, 8 points Autonomous. Male: 0 point Total Dependence, 1 point Severe, 2- 3 points Moderate, 4 points mild, 5 points Autonomous). Measurement time: start, weeks 52 and 78. 7. Psycho-behavioral manifestations. Measures by NPI (Maximum score 120 points. The higher the score, the worse the patient is). Measurement time: start, weeks 52 and 78. 8. Degree of depression. Measured by the Cornell scale (Less than 12 points: No depression. 12 to 24 points: Minor or mild depression. 25 or more points: Major depression). Measurement time: start, weeks 52 and 78. 9. Brain perfusion. Measured by SPECT (Significant increase: Increase greater than 10%. Slight increase: Increase 5-10% in some regions, keeping others unchanged. No change: No variation with respect to the initial study. Decrease: Decrease greater than 5%) . Measurement time: start, weeks 78. 10. Glucose metabolism. Measured by FDG-PET(Final-initial change observed in the pattern of hypometabolism of glucose at the loco-regional level in the brain, it will be evaluated if the patient improved, worsened or remained stable). Measurement time: start, weeks 78. 11. Hippocampal atrophy. Measurement by MRI (Variations less than or equal to 4%±2: stable patient). Measurement time: start, week 78. Security related: • Severity of the adverse event (serious, not serious). Measurement time tstart, weeks 52 and 78.. • Type of adverse event (will classify the type of adverse event according to the categories established in Regulation 45 of 2007 of the CECMED). Measurement time start, weeks 52 and 78.. • Intensity of the adverse event (mild, moderate, severe). Measurement time start, weeks 52 and 78.. • Causality of the adverse event (definite, very likely, likely, possible, unlikely, unrelated, not evaluable). Measurement time start, weeks 52 and 78.. • Attitude towards the drug (no changes, dose modification, temporary or definitive interruption). Measurement time start, weeks 52 and 78. • Outcome (recovered, recovered with sequelae requiring treatment, recovered with sequelae not requiring treatment, death). Measurement timestart, weeks 52 and 78. • Hemoglobin (According to the values stipulated in each center). Measurement time: start, weeks 52 and . • Hematocrit (According to the values stipulated in each center). Measurement time: start, weeks 52 and . • Platelet count (According to the values stipulated in each center). Measurement time: start, weeks 52 and . • White blood cell count (According to the values stipulated in each center). Measurement time: start, weeks 52 and . • Glycaemia (According to the values stipulated in each center). Measurement time: start, weeks 52 and . • Glutamic oxalacetic transaminase (GOT) (According to the values stipulated in each center). Measurement time: start, weeks 52 and . • Glutamic-pyruvic transaminase (GTP) (According to the values stipulated in each center). Measurement time: start, weeks 52 and . • Cholesterol (According to the values stipulated in each center). Measurement time: start, weeks 52 and . • Triglycerides (According to the values stipulated in each center). Measurement time: start, weeks 52 and . • Creatinine (According to the values stipulated in each center). Measurement time: start, weeks 52 and . • Uric acid (According to the values stipulated in each center). Measurement time: start, weeks 52 and . • ECG (Normal, Abnormal). Measurement time: start, weeks 52 and 78

Selection criterias

Section to complete information about the inclusion and exclusion criteria for participant selection, including age and gender.

Gender:

Male/Female

Minimum age:

50 years

Maximum age:

None

Inclusion criteria:

1. Patients and/or caregivers who give their consent to participate in the study by signing the informed consent form. 2. Patient with a caregiver physically and mentally able to understand the study and willing to collaborate with the research. 3. Patients aged ≥ 50 years. 4. Patients with GDS from 3 to 5 points, inclusive. 5. Patients with a CDR of 1 to 2 points, inclusive. 6. ADAScog11 score from 16 to 30 points, inclusive. 7. Patients with patent airways.

Exclusion criteria:

1. Medical condition (not Alzheimer's disease) that may be contributing to cognitive impairment in the subject (substance abuse, AIDS, syphilis, stroke or other cerebrovascular disease, head trauma, brain tumor, psychiatric illness). 2. History of unstable angina, acute myocardial infarction, cancer, Parkinson's disease, coagulation disorders, anemia, and chronic/decompensated liver or kidney disorders. 3. Any contraindication that does not allow MRI, SPECT-CT or PET-CT to be performed. 4. Subjects receiving treatment with antipsychotics, barbiturates, monoamine oxidase inhibitors, benzodiazepines and antidepressants, at doses that may compromise neuropsychological tests. 5. Patients who are receiving any of the medications approved for Alzheimer's disease (donepezil, rivastigmine, galantamine, memantine, aducanumab, NeuralCIM) 6. Patients with a history of hypersensitivity to hr-EPO or any component of the product. 7. Patients with known sensitivity to Donepezil hydrochloride, piperidine derivatives or some of the excipients used in the formulation. 8. Alcoholism. 9. Patients receiving treatment with anticoagulants.

Type of population:

Adults

Type of participant:

Patients

Study design

Section to complete information about the characteristics of the study design.

Type study:

Interventional

Purpose:

Treatment

Allocation:

Randomized controlled trial

Masking:

Open

Control group:

Active

Study design:

Other

Other design:

It will be a phase III clinical study, prospective, controlled with donepezil, unbalanced, adaptive (combination of stages, group closure with low probability of success (<0.1) or high toxicity, group closure with high probability (>0.9) of success, if probability of success ≥0.1 and ≤0.9, in both groups the evaluation will be postponed until week 78, the sample size will be readjusted and in the case of the neuroEPO group, its hypothesis will be changed to superiority).

Phase:

Target sample size:

413

Contact for public queries

Section to complete information about Email address, telephone number and postal address of the contact who will respond to general queries, including information about current recruitment status

First Name:

Leslie

Last Name:

Perez Ruiz

Specialty:

Pharmacy degree, PhD

Affiliation:

Center of Molecular Immunology (CIM)

Postal Address:

216 St. & 15 th Ave. Siboney. Playa

City:

Havana

Country:

Cuba

Zip Code:

11600

Telephone:

+537-2143202

Email :

leslie@cim.sld.cu

Contact for scientific queries

Section to complete information about Email address, telephone number and postal address of the contact who will respond to scientific queries.

First Name:

Nelson

Last Name:

Gomez Viera

Specialty:

Second Degree Specialist in Neurology

Affiliation:

Hermanos Ameijeiras Hospital (HHA)

Postal Address:

San Lazaro St. 701 and Belascoain

City:

Havana

Country:

Cuba

Zip Code:

10400

Telephone:

+53-78761821

Email :

ngv@infomed.sld.cu

Research Ethics Committees

Section to complete the data related to the review ethics committees.

Name of Research Ethics Committees:

Hermanos Ameijeiras Surgical Clinical Hospital (centralized)

National Institute of Neurology and Neurosurgery (INN)

International Center for Neurological Restoration

Surgical Medical Research Center (CIMEQ)

Comandante Manuel Fajardo Surgical Clinical Teaching Hospital

Dr. Salvador Allende Teaching Surgical Clinical Hospital

Ibero-Latin American Center for the Elderly (CITED)

Enrique Cabrera General Teaching Hospital

Dr. Carlos J. Finlay Military Hospital

Cristobal Labra Teaching Polyclinic

Cuban Neuroscience Center (CNEURO)

Directorate of Clinical Research of the Isotopes Center

Status of evaluation:

In Evaluation

Status of evaluation date of Ethic Committee:

29/07/2022

Postal address of Ethic Committee :

San Lazaro 701 esq. a Belascoain, Centro Habana, La Habana. Cuba. CP 10400

Calle D y 29. Vedado. Plaza de la Revolución. La Habana. Cuba. CP 10400

Calle 216 esq. 13. Siboney, Playa, La Habana. Cuba

Calle 216 y 11-B, Reparto Siboney, Playa. La Habana. Cuba.

Calle D, e/. 29 y Zapata, Vedado, Plaza de la Revolución. La Habana. Cuba. CP. 10 400.

Calzada del Cerro 1551 esq. Domínguez, Cerro, La Habana. Cuba. CP 12000.

Calle G y 27, Vedado, Plaza. La Habana. Cuba. CP 10400.

Calzada de Aldabo No.11117 Esquina E, Altahabana. Boyeros. La Habana. Cuba. CP 10 800.

Ave 31 y 114, Marianao. La Habana. Cuba. CP 11400.

Ave 51 # 20023. La Lisa. La Habana, Cuba. CP 17100.

Calle 190, No. 19818 e/ Ave 25 y Ave. 27, Playa, La Habana. Cuba.

Calle 34 No. 4501 e/ 45 y 47, Kolhy. Playa. La Habana, Cuba. CP 11300.

Telephone:

+53-78761000

+53-78383022

+53-72715823

+53-78581000

+53-78352538

+53-78776354

+53-78382146

+53-76446010

+53-72743000

+53-72677268

+53-72637100

+53-72023763

Email:

cenclin@hha.sld.cu

aceiriz@infomed.sld.cu

yricardodelafe@gmail.com

investigaciones@cimeq.sld.cu

emilio.zayas@infomed.sld.cu

anniaduany@infomed.sld.cu

niurkacascudo@gmail.com

isamon@infomed.sld.cu

hfinlayza@infomed.sld.cu

lili620809@gmail.com

evelio.gonzalez@cneuro.edu.cu

yamicuba2014@gmail.com

About study completion

Section to complete the data related to the study completion.

Final enrolment number:

243

Study completion date:

15/03/2025

Date of available results:

30/05/2025

Date of first publication:

30/09/2025

Registration and Update

Section to complete information about the name of Primary Registry, date of registration and the unique ID number assigned by the registry (RPCEC).

Primary registry:

RPCEC

Unique ID number:

RPCEC00000409

Date of Registration in Primary Registry:

20/09/2022

Record Verification Date:

2024/06/04

Next update date:

2025/06/04

Link to the spanish version:

Click here

Registered Trials

Registration process

NeuroEPO in mild-moderate Alzheimer's disease

About the RPCEC

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