ThalassemiaPhase 4NCT03392298
Study on the Mechanism of Colla Corri Asini in the Treatment of Thalassemia Patients With Pregnancy Anemia
A Phase 4 study testing Colla corii asini in people with Thalassemia and Pregnancy, run by The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine at 1 site in China.
Trial summary
This study aims to explore the pathways and targets of regulating globin expression, which might be related to Colla corii asini (CCA, E'jiao) treating anemia in pregnant women with β-thalassemia. Read more about this study
- Who is it for?
- Ages 20 to 50 years, women only
- Conditions the study is for
- Thalassemia, Pregnancy
- What is being tested?
- Colla corii asini
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteChina
- Study dates
- 1 Dec 2017to 28 Feb 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 50 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Pregnant women diagnosed as minor or intermediate β-thalassemia by genetic tests;
- 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.
Who cannot join
- 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;
- Patients having received hemopoietic factors or treated by hematopoietic stem cell transplantation in the last 2 months;
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- 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;
- 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.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
the first affiliated hospital of Guangzhou University of Chinese Medicine
Guangzhou, Guangdong, 510405
Yanfang Li, PhD, +86-20-36598857, gzyanfangli@hotmail.com
Song-ping Luo, professor, 13005156625, songpingluo@hotmail.com
About this study
Official title: Investigation of Signal Pathway Induced by Colla Corri Asini Regulating Globin Level in Beta Thalassemia Patients With Pregnancy Anemia
This study aims to explore the pathways and targets of regulating globin expression, which might be related to Colla corii asini (CCA, E'jiao) treating anemia in pregnant women with β-thalassemia. Firstly, ten pregnant patients who meet inclusion criteria will be randomly assigned to either the treatment group or control group in a 1: 1 ratio. The patients in the treatment group will be given 15 g of CCA daily for 4 weeks and followed up, while the control group will be treated with nothing and followed up in the same period. The transcriptional test and bioinformatics analysis would be conducted to detect and determine the potential pathways and targets of regulating globin expression before and after the treatment. Secondly, sixty pregnant patients who meet inclusion criteria will be randomly assigned to either the treatment group or control group in a 2: 1 ratio. The treatment group and control group respectively received the same treatment and follow-up regimen as the transcriptional study mentioned above. According to the results of the transcriptional study, the target gene signaling pathway molecules, Hb concentration, and the levels of α-、β-、γ- and δ-globin will be detected and compared.
Read the detailed 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 after pregnancy, anemia in β-thalassemia patients tends to turn more serious, the risk of adverse pregnancy outcomes accordingly increase. Currently, no consensus has been reached in treating pregnant thalassemia patients due to lack of safe and effective treatment. Regulation of globin gene expression is the key link of β-thalassemia treatment, but the accessible western medicines have many limitations, including bone marrow suppression, carcinogenicity and teratogenicity, and are not suitable for pregnant patients.
In China, 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.
Our previous clinical study showed that CCA can significantly increase the level of hemoglobin and adult hemoglobin (HbA,α2β2) in the pregnant women with β-thalassemia, it was speculated that CCA might induce β globin gene expression, which would be more beneficial to pregnant women than the γ globin gene inducer. But its regulatory pathway is not clear.
This study is designed to explore the pathways and targets of regulating globin expression by using the transcriptomics method, which might be related to CCA treating pregnant anemia in β-thalassemia patients. And then the results of transcriptomics study will be further verified by expanding the clinical samples and implementing cell experiments, aiming to explore the mechanisms of CCA in treating β-thalassemia with pregnant anemia by regulating globin expression.
- Conditions
- Thalassemia, Pregnancy
- Being tested
- Colla corii asini
- Keywords
- Thalassemia, Pregnancy, Globin expression, Colla corii asini
- Medical subject headings
- Thalassemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Colla corii asiniDrug
Also called donkey-hide gelatin
15g Colla corii asini granule, once daily for 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| CCA group | Experimental | Participants in CCA group will be treated with 15g of Colla corii asini granule( produced by Dong-E E-Jiao Co., Ltd)， once daily for 4 weeks. Receives: Drug: Colla corii asini |
| Control group | No intervention | Participants in Control group will be treated with nothing, but followed up for 4 weeks. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hemoglobin(Hb)
the change of hemoglobin(g/L)
Measured: baseline and week 4
Secondary outcomes (2)
the level of α-、β-、γ- and δ-globin mRNA
the change of α-、β-、γ- and δ-globin mRNA(cycle threshold value)
Measured: baseline and week 4
target gene signaling pathway molecules
the change of gene expression level(fold change)
Measured: baseline and week 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2018
- Study start1 Dec 2017
- Primary completion31 Dec 2018 (estimated)
- Study completion28 Feb 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for ThalassemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- National Natural Science Foundation of China
- Responsible party
- Principal investigator, Yanfang Li, The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine
- Investigators
- Yanfang Li, PhD, Principal investigator, the first affiliated hospital of Guangzhou University of Chinese Medicine, Guangzhou
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03392298
- Sponsor's protocol ID
- TH-3
- Status last verified
- Dec 2017
- First submitted
- 2 Jan 2018
- Last updated
- 16 Jan 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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. doi: 10.1007/s12185-016-2069-0. Epub 2016 Jul 25.
PubMed 27456464Cheng 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.
PubMed 26949404
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of Signal Pathway Induced by Colla Corri Asini Regulating Globin Level in Beta Thalassemia Patients With Pregnancy Anemia
- ClinicalTrials.gov ID
- NCT03392298
- Acronym / sponsor ID
- TH-3
- Conditions
- Thalassemia, Pregnancy
- Keywords
- Thalassemia, Pregnancy, Globin expression, Colla corii asini
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- The First Affiliated Hospital, Guangzhou University of Traditional Chinese MedicineUniversity, hospital or other
- Collaborators
- National Natural Science Foundation of China
- Study start
- 1 Dec 2017 (actual)
- Primary completion
- 31 Dec 2018 (estimated)
- Study completion
- 28 Feb 2019 (estimated)
- First posted
- 5 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims to explore the pathways and targets of regulating globin expression, which might be related to Colla corii asini (CCA, E'jiao) treating anemia in pregnant women with β-thalassemia. Firstly, ten pregnant patients who meet inclusion criteria will be randomly assigned to either the treatment group or control group in a 1: 1 ratio. The patients in the treatment group will be given 15 g of CCA daily for 4 weeks and followed up, while the control group will be treated with nothing and followed up in the same period. The transcriptional test and bioinformatics analysis would be conducted to detect and determine the potential pathways and targets of regulating globin expression before and after the treatment. Secondly, sixty pregnant patients who meet inclusion criteria will be randomly assigned to either the treatment group or control group in a 2: 1 ratio. The treatment group and control group respectively received the same treatment and follow-up regimen as the transcriptional study mentioned above. According to the results of the transcriptional study, the target gene signaling pathway molecules, Hb concentration, and the levels of α-、β-、γ- and δ-globin will be detected and compared.
Detailed 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 after pregnancy, anemia in β-thalassemia patients tends to turn more serious, the risk of adverse pregnancy outcomes accordingly increase. Currently, no consensus has been reached in treating pregnant thalassemia patients due to lack of safe and effective treatment. Regulation of globin gene expression is the key link of β-thalassemia treatment, but the accessible western medicines have many limitations, including bone marrow suppression, carcinogenicity and teratogenicity, and are not suitable for pregnant patients.
In China, 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.
Our previous clinical study showed that CCA can significantly increase the level of hemoglobin and adult hemoglobin (HbA,α2β2) in the pregnant women with β-thalassemia, it was speculated that CCA might induce β globin gene expression, which would be more beneficial to pregnant women than the γ globin gene inducer. But its regulatory pathway is not clear.
This study is designed to explore the pathways and targets of regulating globin expression by using the transcriptomics method, which might be related to CCA treating pregnant anemia in β-thalassemia patients. And then the results of transcriptomics study will be further verified by expanding the clinical samples and implementing cell experiments, aiming to explore the mechanisms of CCA in treating β-thalassemia with pregnant anemia by regulating globin expression.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CCA group | Experimental | Drug: Colla corii asiniParticipants in CCA group will be treated with 15g of Colla corii asini granule( produced by Dong-E E-Jiao Co., Ltd)， once daily for 4 weeks. |
| Control group | No intervention | –Participants in Control group will be treated with nothing, but followed up for 4 weeks. |
Who may qualify
- Ages
- 20 to 50 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Pregnant women diagnosed as minor or intermediate β-thalassemia by genetic tests;
- 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;
Key exclusion criteria (12 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Colla corii asiniAlso: donkey-hide gelatin15g Colla corii asini granule, once daily for 4 weeks | Drug | CCA group |
Primary outcome
Hemoglobin(Hb)
Time frame: baseline and week 4
the change of hemoglobin(g/L)
2 secondary outcomes
the level of α-、β-、γ- and δ-globin mRNA
Time frame: baseline and week 4
target gene signaling pathway molecules
Time frame: baseline and week 4
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2018.
- Background: PubMed 27456464Li 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. doi: 10.1007/s12185-016-2069-0. Epub 2016 Jul 25.
- Background: PubMed 26949404Cheng 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yanfang Li, PhD principal investigator
the first affiliated hospital of Guangzhou University of Chinese Medicine, Guangzhou
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Colla corii asini in people with Thalassemia and Pregnancy, run by The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 16 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yanfang Li, PhD (+86-20-36598857, gzyanfangli@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hemoglobin(Hb) (time frame: baseline and week 4). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03392298, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jan 2018.