Colla Corii Asini Treating Anemia in Pregnant Women With Thalassemia(Presenting the Syndrome of Blood Deficiency)

Thalassemia Clinical Trial

Official title:

A Multi-center Randomized, Double-blind, Placebo-controlled Study of Colla Corii Asini for the Treatment of Anemia in Pregnant Women With Thalassemia(Presenting the Syndrome of Blood Deficiency)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03374111
• Other study ID #: TH-2
• Status: Recruiting
• Phase: Phase 4
• Start date: March 1, 2018
• Est. completion date: December 30, 2019

Study information

• Verified date: December 2018
• Source: The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine
• Contact: Song-ping Luo, PhD
• Phone: 13005156625
• Email: songpingluo[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

480 pregnant patients diagnosed of silent or standard α-thalassemia, HbH disease, minor or intermediate β-thalassemia with mild anemia will be randomly assigned to treatment group and control group. Patients in the treatment group will be given 15 g of Colla corii asini powder form daily for 8 weeks and followed up to 42 days postpartum while the control group will be observed and followed up in the same period treated with placebo. Levels of hemoglobin(Hb), reticulocyte (RET), immaturity reticulocyte (IRF), indirect bilirubin(IBIL), total bilirubin(TBIL), lactic dehydrogenase(LDH) will be measured on three visits(baseline, week 4 and week 8). The curative effect of TCM Syndrome( week 8) and undesirable pregnancy outcomes(42 days after giving birth) will be observed.

Description:

Thalassemia is a type of hemolytic anemia disease caused by genetic defect of synthesis in one or more globin chains. Among all the single genetic disorders thalassemia has the highest incidence rate in the world and causes heavy burdens on public health system. In China, the southern provinces suffer from high incidence of thalassemia, which is particularly common in the population of Guangdong, Guangxi and Yunnan provinces. Epidemiological studies showed that in Guangdong alone about 17.83 % of the 14,332 pregnant women across 21 regions examined were diagnosed as carriers of thalassemia .

Recent studies showed that compared with healthy controls, women with thalassemia are associated with a wide range of abnormality and adverse pregnancy outcomes including cardiovascular disease, thrombotic disease, spontaneous miscarriage, premature delivery, oligohydramnios, fetal growth restriction and low birth weight. Currently there is no consensus on treating anemia in pregnant thalassemia patients. Due to the absence of an safe and effective therapeutic measures， many thalassemia patients are prone to develop low level of Hb, which can severely impact the fetal growth and maternal health.

In traditional Chinese medicine (TCM), Colla corii asini (CCA, E'jiao) is a gelatin-like traditional Chinese medicine refined from donkey hide and has been widely used in clinical antanemic therapy for more than 2000 years. In the last decade, many studies had addressed the effect of CCA on the anemia using modern pharmacological approaches. The results indicated that CCA contains collagen protein,glycogen and a variety of trace elements, a variety of amino acids, etc. the main components of CCA can promote hematopoiesis by a number of mechanisms which eventually increase the peripheral erythrocyte counts and Hb concentration. Therefore, the investigators proposed that the hematopoietic effects of CCA might also contribute to the treatment of thalassemia with insuffcient or abnormal Hb concentration.

The study aims to evaluate the efficacy and safety of Colla corii asini (CCA ) in improve anemia during pregnancy among silent or standard α-thalassemia, HbH disease, minor or intermediate β-thalassemia. Four hundred and eighty pregnant patients who meet inclusion criteria will be randomly assigned to either the treatment group or control group. Patients in the treatment group will be given 15 g of CCA daily for 8 weeks and followed up to 42 days postpartum, while the control group were observed and followed up in the same period treated with placebo. Levels of hemoglobin (Hb),reticulocyte (RET), immaturity reticulocyte (IRF), indirect bilirubin (IBIL), total bilirubin (TBIL), lactic dehydrogenase (LDH) will be measured on three visits (baseline, week 4 and week 8). The curative effect of TCM Syndrome( week 8) and undesirable pregnancy outcomes(42 days after giving birth) will be observed.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 480
• Est. completion date: December 30, 2019
• Est. primary completion date: October 1, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 50 Years

Eligibility

Inclusion Criteria:

• Pregnant women diagnosed as thalassemia carriers by genetic test with clinical presentation of silent or standard a-thalassemia, HbH disease, minor or intermediate ß-thalassemia;

• Patients with mild anemia (70 g/L= Hb<100 g/L) prior to study enrollment;

• Singleton pregnancy ;

• Gestational age between 24-32 weeks;

• Patients having not received blood transfusion in the last 12 weeks;

• Written informed consent of the patient.

Exclusion Criteria:

• Known history of allergy or reaction to any component of the investigational product;

• Allergic to two or more drugs;

• Patients with severe thalassemia;

• Anaemia not caused by thalassemia (e.g., iron deficiency, aplastic, megaloblastic or haemolytic anaemia) or bone marrow diseases, leukemia.

• Twin or multiple pregnancies;

• Placental Abnormality (e.g., placenta previa, multilobate placenta, placenta succenturiate, placenta cirumvallate) or polyhydramnios, oligohydramnios, fetal growth restriction, fetal anomaly;

• Patients having received hemopoieticfactors or treated by hematopoietic stem cell transplantation in the last 2 months;

• Hypersplenism or hypertensive disorder in pregnancy;

• Patients with any of the following abnormalities: immunodeficiency, primary diseases involving cardiovascular system, liver, kidney, gastrointestinal tract, endocrine system and hematological system;

• 1.5 times or more higher plasma creatinine level than high limit of normal state;

• 1.5 times or more higher AST or ALT than high limit of normal state;

• Patients with mental illness;

• Patients who suffer from drug or alcohol abuse;

• Patients who addicted to smoking and drinking;

• Participation in any clinical investigational drug study within the previous 3 months;

• Patients who are regarded as ineligible for this study by investigator.

Related Conditions & MeSH terms

• Anemia
• Thalassemia

Intervention

Drug:
• Colla corii asini
15 g Colla corii asini granule daily for 8 weeks
• a Simulate Agent of Colla corii asini granule
15 g a Simulate Agent of Colla corii asini granule daily for 8 weeks

Locations

Country	Name	City	State
China	The third people's Hospital of Dongguan	Dongguan	Guangdong
China	Department of Gynaecology and Obstetrics,Nanfang Hospital, Southern Medical University	Guangzhou	Guangdong
China	Dongguan Guangji Hospital	Guangzhou	Guangdong
China	Intranet of Guangzhou Women and Children's Medical Center	Guangzhou	Guangdong
China	The Fifth Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong
China	the first affiliated hospital of Guangzhou University of Chinese Medicine	Guangzhou	Guangdong
China	The First Affiliated Hospital of Jinan University	Guangzhou	Guangdong
China	Liuzhou Municipal Matemal and Child Health Hospital	Liuzhou	Guangxi
China	Ruikang Hospital of Guangxi University of Traditional Chinese Medicine	Nanning	Guangxi
China	The First Affiliated Hospital of Guangxi University of Chinese Medicine	Nanning	Guangxi
China	The Guangxi Zhuang Autonomous Region National Hospital	Nanning	Guangxi
China	Shenzhen maternity and child health care hospital	Shenzhen	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine

Country where clinical trial is conducted

China, 

References & Publications (2)

Cheng YL, Zhang XH, Sun YW, Wang WJ, Fang SP, Wu ZK. Clinical Effect and Mechanism of Yisui Shengxue Granules in Thalassemia Patients with Mild, Moderate, or Severe Anemia. Evid Based Complement Alternat Med. 2016;2016:1713897. doi: 10.1155/2016/1713897. Epub 2016 Feb 2. — View Citation

Li Y, He H, Yang L, Li X, Li D, Luo S. Therapeutic effect of Colla corii asini on improving anemia and hemoglobin compositions in pregnant women with thalassemia. Int J Hematol. 2016 Nov;104(5):559-565. Epub 2016 Jul 25. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hemoglobin(Hb)	the change of hemoglobin(g/L)	baseline, week 4 and week 8
Secondary	reticulocyte (RET)	the change of reticulocyte (RET)count(×10^9/L)	baseline, week 4 and week 8
Secondary	immature reticulocyte fraction(IRF)	the change of immature reticulocyte fraction(%)	baseline, week 4 and week 8
Secondary	adverse event	undesirable pregnancy outcomes	tracked for 42 days after giving birth
Secondary	indirect bilirubin(IBIL)	the change of indirect bilirubin(IBIL)(µmol/L)	baseline, week 4 and week 8
Secondary	total bilirubin(TBIL)	the change of total bilirubin(TBIL) (µmol/L)	baseline, week 4 and week 8
Secondary	lactic dehydrogenase(LDH)	the change of lactic dehydrogenase(LDH)(U/L)	baseline, week 4 and week 8
Secondary	anaemia cure rates	anaemia cure rates(%):The concentration of hemoglobin was higher than baseline > 5g/L;The improvement rate = improved cases/the total number of cases * 100%	week 8
Secondary	The curative effect of TCM Syndrome	the change of the TCM syndrome scores of two groups before and after treatment(%)	week 8