Clinical Trial to Evaluate the Potential Efficacy and Safety of Human Umbilical Cord Blood and Plasma

Aging Clinical Trial

Official title:

A Randomized, Double-blinded and Placebo-controlled Pilot Clinical Trial to Evaluate the Potential Efficacy and Safety of Human Umbilical Cord Blood and Plasma by Clinical Markers of Frailty in Adult Who Defined Pre-Frailty

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02418013
• Other study ID #: CHAIRB_BD_V.5.1_F011
• Status: Active, not recruiting
• Phase: Phase 1
• First received: March 26, 2015
• Last updated: January 11, 2016
• Start date: March 2015
• Est. completion date: August 2017

Study information

• Verified date: January 2016
• Source: Bundang CHA Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study aims to carry out a safety evaluation of human cord blood and frozen plasma as treatment for pre-frailty , to assess whether the treatment can prevent and improve the aging process, and to identify useful clinical markers of frailty.

The study is a randomized, double-blinded and placebo-controlled pilot clinical Trial conducted at CHA clinical trial institute.

Description:

Assessment criteria for the study include (1) clinical indicators-weight loss, a decrease in physical activity, weak grip strength, depression; (2) Short Physical Performance Battery(SPPB); (3) SF-36; (4)cardiac output; (4)biomarkers for oxidative stress, inflammation and immune response; (5) methylation; (6) mitochondria DNA copy number; (7) growth factors; (8) antioxidant capacity; (9) hormone assay; (10) genome assay; (11) metabolite; (12) safety of intravenous administration.

Participants will be randomly assigned to three experimental groups and one control group in a ratio of 1:1:1:1. At second visit, the participants will be administered with experimental and placebo agents. Follow-up visits are expected to be at 7 days, 1 and 6 months after the first treatment. Sixth visit is the completion of it.

Primary end points are defined as severe clinical abnormalities, which could be observed until 1 month after administration of blood-derived products, including death, pulmonary embolism, stroke, respiratory stress and hospitalization due to abnormal findings in laboratory tests.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 64
• Est. completion date: August 2017
• Est. primary completion date: August 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 55 Years and older

Eligibility

Inclusion Criteria:

1. Diagnosis of pre-frailty

2. One or two scores in Simple FRAIL questionnaire

3. Aged 55 or over

4. Willing and able to be hospitalized according to the research plan

5. Able to participate in our research during 12 months

6. For women, they must be diagnosed with menopause or infertility

Exclusion Criteria:

1. Diagnosis of being irreversible disabled

2. Dementia or cognitive impairment clinically relevant to it

3. Unable to perform tasks required for analysis of primary end point

4. Scheduled to receive organ transplantation

5. Hemoglobin < 8 g/dl; white blood cells count <3000/mm3; absolute Neutrophil count < 500/dl; Thrombocyte count <80,000/mm3; , AST/ALT or ALP > 3 times the normal level

6. Hemoglobin >17g/dl for male and >16 g/dl for female

7. Diagnosis of cancer within 5 years or having the possibility to contract cancer

8. Anticancer chemotherapy and radiation therapy

9. History (within 6 months) of acute diseases such as myocardial infarction, unstable angina, stroke, bone fracture

10. Hormone therapy within 6 months

11. Recent and current use of Immunosuppressive drug or HIV patients

12. History of hospitalization due to infectious disease such as pneumonia within one year

13. Previous (within one months) or current participants in other clinical trials

14. Severe kidney (eGFR< 30) and heart failure (Class III/IV)

15. Any participants who, in the opinion of the investigators, are considered to have safety problems and/or not to perform tasks successfully

16. History of drug or alcohol abuse

17. Chronic Hepatitis B or C: history taking

18. Known or suspected pregnancy (Women must be subjected to pregnancy test)

19. Hypersensitive to dimethyl sulfoxide(DMSO)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Aging

Intervention

Other:
• Fresh cord blood(experimental group A)
Cord blood is administered through intravenous at CHA clinical trail institute. Chlorpheniramine maleate at the concentration of 0.6ml/10kg is administered prior to the treatment.
• Frozen cord blood(experimental group B)
Cord blood is administered through intravenous at CHA clinical trail institute. Chlorpheniramine maleate at the concentration of 0.6ml/10kg is administered
• Frozen plasma(experimental group C)
Cord blood is administered through intravenous at CHA clinical trail institute. Chlorpheniramine maleate at the concentration of 0.6ml/10kg is administered
• Placebo group
A placebo agent is administered through intravenous at CHA clinical trail institute. It should be certain that when administered, participants are not aware of which treatments are preformed.

Locations

Country	Name	City	State
Korea, Republic of	Bundang CHA hospital	Seong nam	Bundanggu

Sponsors (1)

Lead Sponsor	Collaborator
Bundang CHA Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in scores of Short Physical Performance Battery (SPPB) as a measure of efficacy for anti-aging effects	The investigators will assess changes in scores from baseline at 7 days after transplantation. After normality test, either unpaired t-test or wilcoxon rank sum test will be conducted.	7 days after transplantation	No
Secondary	Hand grip strength (in kg) as a measure of efficacy for anti-aging effects	The test is scheduled to be conducted at the day of transplantation and at 1 week , 1 month, 6 months after the treatments. After normality test on the average difference, either unpaired t-test or wilcoxon rank sum test will be conducted for statistical analysis.; The followings are diagnosis criteria for frailty based on hand grip strength(in kg): Male; equal or less than 18 kg for the participants with BMI (body mass index)=21.89; equal or less than 23 kg for the participants with 22.02 equal or less than 21.5 kg for the participants with 23.67equal or less than 25 kg for the participants with BMI>24.88; Female; equal or less than 12.2 kg for the participants with BMI (body mass index)=22.52; equal or less than 13 kg for the participants with 22.53equal or less than 14.5 kg for the participants with 24.24equal or less than 13 k	6 months period after transplantation	No
Secondary	SF_36(The Short Form (36) Health Survey) as a measure of improvement in the quality of life	The test is scheduled to be conducted at the day of transplantation (2nd visit) and at 1 week (3rd visit), 1 month (4th visit), 6 months (5th visit) after the treatments. The investigators will assess changes compared to baseline which will be measured at the day of transplantation. After normality test on the average difference, either unpaired t-test or wilcoxon rank sum test will be conducted for statistical analysis.	6 months period after transplantation	No
Secondary	Biomarkers for oxidative stress and inflammation as a measure of efficacy for anti-aging effects	The test is scheduled to be conducted at the day of transplantation (2nd visit) and at 1 week (3rd visit), 1 month (4th visit), 6 months (5th visit) after the treatments. Changes in biomarkers such as CRP, IL-1,6, IL-10, LIF, D-dimer, fibrinogen, TNF-a, CBC with differential, malondialdehyde, 4-hydroxynonenal will be assessed. After normality test on the average difference, either unpaired t-test or wilcoxon rank sum test will be conducted for statistical analysis.	6 months period after transplantation	No
Secondary	Biomarkers for immune response as a measure of efficacy for anti-aging effects	The test is scheduled to be conducted at the day of transplantation (2nd visit) and at 1 week (3rd visit), 1 month (4th visit), 6 months (5th visit) after the treatments. The investigators will assess changes of the immune-related biomarkers compared to baseline which will be measured at the day of transplantation. After normality test on the average difference, either unpaired t-test or wilcoxon rank sum test will be conducted for statistical analysis.; Followings are immune markers to be tested; -Eotaxin, FGF-2,Flt-3 Ligand ,Fractalkine,G-CSF, GM-CSF, GRO, IFNa2, IFNr, IL-1a, IL-1b, IL-1ra, IL-2, IL-3, IL-4 ,IL-5 ,IL-6 ,IL-7, IL-8, IL-9, IL-10, IL-12(p40), IL-12(p70), IL-13, IL-15, IL-17, IP-10, MCP-1, MCP-3, MDC, MIP-1a, MIP-1b, PDGF-AA, PDGF-AB/BB, RANTES, sCD40L, sIL-2Ra TGFa, TNFa,TNFb, VEGF	6 months period after transplantation	No
Secondary	Adrenal cortical hormone levels as a measure of efficacy for anti-aging effects	The test is scheduled to be conducted at the day of transplantation (2nd visit) and at 1 week (3rd visit), 1 month (4th visit), 6 months (5th visit) after the treatments. The investigators will assess changes in hormone levels compared to baseline which will be measured at the day of transplantation.; After normality test on the average difference, either unpaired t-test or wilcoxon rank sum test will be conducted for statistical analysis.	Up to 6 months after transplantation	No
Secondary	Telomere length as a measure of efficacy for anti-aging effects	The test is scheduled to be conducted at the day of transplantation (2nd visit) and at 1 week (3rd visit), 1 month (4th visit), 6 months (5th visit) after the treatments. Whether the treatments protect telomere from shortening will be investigated through the comparison analysis.; After normality test on the average difference, either unpaired t-test or wilcoxon rank sum test will be conducted for statistical analysis.	6 months period after transplantation	No
Secondary	Body composition as a measure of efficacy for anti-aging effects	The test is scheduled to be conducted at the day of transplantation (2nd visit) and at 1 week (3rd visit), 1 month (4th visit), 6 months (5th visit) after the treatments. The investigators will assess changes of body composition compared to baseline which will be measured at the day of transplantation.; After normality test on the average difference, either unpaired t-test or wilcoxon rank sum test will be conducted for statistical analysis.	6 months period after transplantation	No
Secondary	Aging-related genetic and epigenetic markers as a measure of efficacy for anti-aging effects	The test is scheduled to be conducted at the day of transplantation (2nd visit) and at 1 week (3rd visit), 1 month (4th visit), 6 months (5th visit) after the treatments. The investigators will assess changes of aging-related genetic markes (e.g ELOVL2. ) compared to baseline which will be measured at the day of transplantation.; After normality test on the average difference, either unpaired t-test or wilcoxon rank sum test will be conducted for statistical analysis.	6 months period after transplantation	No
Secondary	mitochondria DNA copy number as a measure of efficacy for anti-aging effects	The test is scheduled to be conducted at the day of transplantation (2nd visit) and at 1 week (3rd visit), 1 month (4th visit), 6 months (5th visit) after the treatments. Mitochondria DNA copy number of participants will be compared among the treatment groups.; After normality test on the average difference, either unpaired t-test or wilcoxon rank sum test will be conducted for statistical analysis.	6 months period after transplantation	No
Secondary	Aging-related growth factors(GDF11, GDF15, Myostatin) as a measure of efficacy for anti-aging effects	The test is scheduled to be conducted at the day of transplantation (2nd visit) and at 1 week (3rd visit), 1 month (4th visit), 6 months (5th visit) after the treatments. The investigators will assess changes compared to baseline which will be measured at the day of transplantation. The factors will be compared among the treatment groups. After normality test on the average difference, either unpaired t-test or wilcoxon rank sum test will be conducted for statistical analysis.	6 months period after transplantation	No
Secondary	DNA damage extent (8-hydroxyguanine level) as a measure of efficacy for anti-aging effects	The test is scheduled to be conducted at the day of transplantation (2nd visit) and at 1 week (3rd visit), 1 month (4th visit), 6 months (5th visit) after the treatments. The investigators will assess changes of 8-hydroxyguanine in white blood compared to baseline which will be measured at the day of transplantation.; After normality test on the average difference, either unpaired t-test or wilcoxon rank sum test will be conducted for statistical analysis.	6 months period after transplantation	No
Secondary	Changes in scores of Short Physical Performance Battery (SPPB) as a measure of efficacy for anti-aging effects	The test is scheduled to be conducted at the day of transplantation (2nd visit) and at 1 week (3rd visit), 1 month (4th visit), 6 months (5th visit) after the treatments.; The investigators will assess changes in scores compared to baseline which will be measured at the day of transplantation.; After normality test on the average difference, either unpaired t-test or wilcoxon rank sum test will be conducted for statistical analysis.	6 months period after transplantation	No