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Trial record 2 of 2 for:    NCT02615847

A Phase - IIa - IIb, Trial to Study the Safety, Tolerability and Efficacy of Memantine as a Long-term Treatment of SCD (MeMAGEN)

This study is not yet open for participant recruitment.
Verified August 2017 by Dr Koren Ariel, HaEmek Medical Center, Israel
Sponsor:
ClinicalTrials.gov Identifier:
NCT03247218
First Posted: August 11, 2017
Last Update Posted: August 22, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Dr Koren Ariel, HaEmek Medical Center, Israel
  Purpose

Symptomatic sickle cell disease (SCD) is worldwide the most frequent cause for hereditary hemolytic anemia with recurrent pain crises. Hemolysis, vaso- occlusive and pain crises are hallmarks of this disease and are causative for an important socio-economic burden worldwide, especially in Africa.

Aside from allogenic stem cell transplantation, which is rarely available and very expensive, at present there is no curative treatment for patients with SCD. The current standard of care includes treatment with Hydroxyurea and symptomatic care such as transfusions, antibiotic/analgesic treatment. Recent findings allowed the investigators to come up with a novel pharmacological target for prophylactic treatment of this group of patients. The investigators showed that N-methyl D-aspartate receptors (NMDARs) are substantially up-regulated in circulating red blood cells (RBCs) of SCD patients. Ca2+ uptake via these non-selective cation channels has major impact on RBC hydration and facilitates polymerization of deoxygenated hemoglobin S variant in RBCs of patients. In vitro observations shows that inhibition of NMDARs with Memantine caused re-hydration and largely prevented hypoxia-induced sickling in RBCs. A pilot trial MemSID (NCT02615847) was conducted in August 2015-March 2017 at the Hematology Division of University Hospital Zurich. A small cohort of adult SCD patients was treated with 20 mg Memantine daily to test safety, tolerability and efficacy of this drug and to assess the effect of Memantine on hemolytic activity and RBC stability. Pilot data reveal safety and an impressive therapeutic potential of Memantine in treating SCD patients. Due to a small number of SCD patients in Switzerland, an extended trial including larger number of adult and adolescent patients will be performed at the Pediatric Hematology Unit of the Emek Medical Center in Afula, Israel


Condition Intervention Phase
Sickle Cell Disease Drug: Memantine Hydrochloride Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Intervention Model Description:
a single center and open label study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase - IIa - IIb, Open Label, Single Center Trial to Study the Safety, Tolerability and Efficacy of Memantine Teva® as Supportive Long-term Treatment in Symptomatic Sickle Cell Disease

Resource links provided by NLM:


Further study details as provided by Dr Koren Ariel, HaEmek Medical Center, Israel:

Primary Outcome Measures:
  • Assessment of Incidence and severity of Memantine treatment-related Adverse Events (AE), including clinically significant abnormal laboratory values in adult and adolescent patients with symptomatic SCD. [ Time Frame: one year ]

    The following laboratory parameters will be assessed and evaluated:

    • Complete blood count.
    • Hemolytic activity (reticulocytes, indirect bilirubin and LDH).
    • Iron status (ferritin, serum iron, transferrin and transferrin saturation).
    • Fetal hemoglobin levels
    • Red cell volume, density, membrane stability, adherablilty, inflammatory markers and metabolic activity.


Secondary Outcome Measures:
  • Assessment of Clinical Improvement during Memantine treatment compared to a pre-screening data obtained from patients clinical files in adult and adolescent patients with symptomatic SCD. [ Time Frame: one year ]

    Clinical improvements will be assessed by

    • Number of hospital days.
    • Number of emergency consultations
    • Impact on working ability (the number of days with inability to work)
    • The amount and type of analgesic medication received by the patient.
    • The amount of RBC transfusions received by the patient.
    • The number of days that antibiotics were prescribed.
    • A questionnaire on quality of life.
    • Evaluation of Cognitive function.


Estimated Enrollment: 40
Anticipated Study Start Date: January 1, 2018
Estimated Study Completion Date: June 30, 2020
Estimated Primary Completion Date: December 1, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single group of patients

In this study 40 patients with SCD will be included. Twenty patients aged 18 years or older (cohort 1) and twenty patients 10 - 17 years old (cohort 2).

All the patients will receive Memantine Teva® film-coated tablets (Memantine hydrochloride) produced by Teva Pharma AG and will be provided as 5 mg, 10 mg, and 20 mg tablets packed in blister.

The study drug will be taken once a day per os, during one year.

Drug: Memantine Hydrochloride
a low-moderate affinity, uncompetitive, NMDAR antagonist
Other Name: Memantine TEVA

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   10 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Documented symptomatic sickle cell disease (HbSS or HbS/beta thalassemia)
  • Age 18 years or older (cohort 1) and 10 - 17 years old (cohort 2)
  • Able and willing to provide written informed consent and to comply with the study protocol procedures Willing to use two effective methods of contraception during study treatment until 6 months after stop of study treatment. Effective contraception methods are considered oral, injectable, implantative contraceptives or intrauterine contraceptive devices combined with use of condom.

Exclusion Criteria:

  • History of transfusion during last three months before Screening
  • Patients with active bacterial, viral or fungal infection requiring systemic treatment
  • Patients with known infection with human immunodeficiency virus (HIV) of human T cell leukemia virus 1 (HTLV-1)
  • Inadequate renal function: creatinine clearance < 30ml/min
  • Inadequate liver function: NCICTC Grade 3 liver function tests (AST, ALT > 5x upper limit of normal (ULN))
  • Patients with Chronic Active Hepatitis - HCV or HBV
  • History of malignancy
  • Women who are pregnant or breast feeding
  • Known epileptic disease and under treatment with anticonvulsive drugs
  • The receipt of any investigational product within 30 days prior to this trial
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03247218


Contacts
Contact: Ariel Koren, Professor 9726495615 ext 5615 koren_a@clalit.org.il
Contact: Anna H Shuman, B.sc 9726494044 ext 4044 annami31@clalit.org.il

Sponsors and Collaborators
HaEmek Medical Center, Israel
Investigators
Principal Investigator: Ariel Koren, Professor Emek Medical Center
  More Information

Responsible Party: Dr Koren Ariel, Head of Pediatric Hematology Unit, HaEmek Medical Center, Israel
ClinicalTrials.gov Identifier: NCT03247218     History of Changes
Other Study ID Numbers: 071-17 EMC
First Submitted: August 1, 2017
First Posted: August 11, 2017
Last Update Posted: August 22, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Memantine
Antiparkinson Agents
Anti-Dyskinesia Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents