Ignite Creation Date:
2024-05-06 @ 10:24 AM
Last Modification Date:
2024-10-26 @ 12:29 PM
Study NCT ID:
NCT03247218
Status:
UNKNOWN
Last Update Posted:
2019-11-01
First Post:
2017-08-01
Brief Title:
A Phase - IIa - IIb Trial to Study the Safety Tolerability and Efficacy of Memantine as a Long-term Treatment of SCD
Sponsor:
HaEmek Medical Center Israel
Organization:
HaEmek Medical Center Israel
Study Overview
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
Status:
UNKNOWN
Status Verified Date:
2019-10
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MeMAGEN
Brief Summary:
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 antibioticanalgesic 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
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 antibioticanalgesic 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
Detailed Description:
Background and Rationale 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 antibioticanalgesic treatment Recent findings allowed the investigators to come up with a novel pharmacological target for prophylactic treatment of this group of patients 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 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
Objectives Primary objective
To evaluate the safety tolerability and efficacy of low doses of Memantine Teva treatment in adult and adolescent patients with symptomatic SCD
Secondary objective
To asses and evaluate the long-term effects of Memantine Teva on the clinical and laboratory parameters in adult and adolescent patients with symptomatic SCD
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 Additional parameters related to red cell volume density membrane stability adherablilty inflammatory markers and metabolic activity will be detected by the external laboratory Red Cell Research Group University of Zurich Study design It is a single center and open label study
Laboratory analysis including hematology coagulation and chemistry test will be performed and urine samples will be also analyzed In addition at each visit a physical examination and measurement of vital signs will be performed
The number of total admissions hospital days and emergency consultations will be recorded The amount and type of analgesic medication given The amount of RBC transfusions the number of days that antibiotics were prescribed will be also recorded
At screening and at the end of the study SCD specific assessments will be performed which include cardiologic examination ECG ECHO abdominal sonography ophthalmological examination lung function testing and neuroangiologic examination
The impact on working ability assessed by the number of days with inability to work For the impact on work ability and social life activities a questionnaire of quality of life will be filled out by the patient once a month
- Evaluation of Cognitive function will be also performed at screening and at the end of the study Study Product Intervention Memantine Teva is a low-moderate affinity uncompetitive NMDAR antagonist and is licensed in Switzerland and in Israel for the treatment of Alzheimer disease
Memantine Teva film-coated tablets Memantine hydrochloride is 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 Number of Participants with Rationale 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
Study Duration The study lasts 15 month per patient
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 antibioticanalgesic treatment Recent findings allowed the investigators to come up with a novel pharmacological target for prophylactic treatment of this group of patients 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 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
Objectives Primary objective
To evaluate the safety tolerability and efficacy of low doses of Memantine Teva treatment in adult and adolescent patients with symptomatic SCD
Secondary objective
To asses and evaluate the long-term effects of Memantine Teva on the clinical and laboratory parameters in adult and adolescent patients with symptomatic SCD
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 Additional parameters related to red cell volume density membrane stability adherablilty inflammatory markers and metabolic activity will be detected by the external laboratory Red Cell Research Group University of Zurich Study design It is a single center and open label study
Laboratory analysis including hematology coagulation and chemistry test will be performed and urine samples will be also analyzed In addition at each visit a physical examination and measurement of vital signs will be performed
The number of total admissions hospital days and emergency consultations will be recorded The amount and type of analgesic medication given The amount of RBC transfusions the number of days that antibiotics were prescribed will be also recorded
At screening and at the end of the study SCD specific assessments will be performed which include cardiologic examination ECG ECHO abdominal sonography ophthalmological examination lung function testing and neuroangiologic examination
The impact on working ability assessed by the number of days with inability to work For the impact on work ability and social life activities a questionnaire of quality of life will be filled out by the patient once a month
- Evaluation of Cognitive function will be also performed at screening and at the end of the study Study Product Intervention Memantine Teva is a low-moderate affinity uncompetitive NMDAR antagonist and is licensed in Switzerland and in Israel for the treatment of Alzheimer disease
Memantine Teva film-coated tablets Memantine hydrochloride is 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 Number of Participants with Rationale 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
Study Duration The study lasts 15 month per patient
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None