Umbilical Cord-Derived Mesenchymal Stem Cell (VCELL 1) for Male Patients With Sexual Deficiency

Sexual Dysfunction Male Clinical Trial

Official title:

Evaluation of the Safety and Efficacy of Umbilical Cord-Derived Mesenchymal Stem Cell (VCELL 1) for Male Patients With Sexual Deficiency: A Phase I/IIa Randomised Crossover Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05345418
• Other study ID #: ISC.21.08
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 1, 2022
• Est. completion date: June 30, 2024

Study information

• Verified date: August 2022
• Source: Vinmec Research Institute of Stem Cell and Gene Technology
• Contact: Phuong Nguyen, MSC
• Phone: +84 914740683
• Email: v.phuongnh9[@]vinmec.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Sexual functional deficiency affects largely the physical conditions, life and sexual quality of the patients. Hypogonadism affects about 4 to 5 million men in the US, and the incidence increases with age. In our recent phase I clinical trial, we have shown that intravenous adipose - derived MSC administration was safe in female and male patients with hormone deficiency. Post-transplantation sexual satisfaction was observed in all patients enrolled in this study. Testosterone levels in males increased significantly after transplantation and were maintained at high levels for up to 6 months before decreasing again at the 12-month follow-up. The aim of this clinical trial was to assess the safety and effectiveness of allogeneic administration of MSCs in middle-aged people with sexual functional deficiency.

Description:

Sexual functional deficiency occurs at some point in life and becomes a problematic issue in middle-aged adulthood. Regenerative medicine, especially mesenchymal stem cell (MSC) transplantation, has developed extensively, with preclinical and clinical trials emphasizing the benefits of stem cell therapy for restoration of sexual deficiency. n our recent phase I clinical trial, we have shown that intravenous adipose - derived MSC administration was safe in female and male patients with hormone deficiency. Post-transplantation sexual satisfaction was observed in all patients enrolled in this study. Testosterone levels in males increased significantly after transplantation and were maintained at high levels for up to 6 months before decreasing again at the 12-month follow-up. The aim of this clinical trial was to assess the safety and effectiveness of allogeneic administration of MSCs in middle-aged people with sexual functional deficiency. In phase II, 40 males with hormone deficiency will be recruited and divided randomly into two groups (n=23 each). The group A will receive UC-MSCs intravenously at day 0 and day 90 ± 7, while the group B will be infused with UC-MSCs at day 180 ± 14 and day 270 ± 14. Each group will be monitored for 365 ± 14 days after the first infusion. The phase II is to investigate safety and efficacy of UC-MSC infusion for the treatment of sexual hormone deficiency in males. The primary outcome are: (1) numbers of AEs or SAEs during UC-MSC infusion and 365 ± 14 days after the first infusion; (2) Testosterone levels and sexual life quality through quantification of Aging Men Symptom (AMS), International Index of Erectile Function (IIEF), and Sexual Quality of Life Questionnaire (SQoL-M) at day 90 ± 7 and day 180 ± 14 of the group A compared to those of the group B. The secondary outcome are: (1) Testosterone levels and (2) sexual life quality through quantification of AMS, IIEF, and SQoL-M at day 90 ± 7, day 180 ± 14, and day 365 ± 14 after the first UC-MSC infusion of each group compared to the baseline; (3) cytokine concentration (TNFa, IFN-γ, IL1, IL-6, IL-8, IL-4, IL-10, IDO) in serum of the participants and their T cell immunophenotype at day 90 ± 7, day 180 ± 14, and day 365 ± 14 after the first UC-MSC infusion.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 158
• Est. completion date: June 30, 2024
• Est. primary completion date: June 1, 2022
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 50 Years to 70 Years

Eligibility

Inclusion Criteria:

• Males with sexual hormone deficiency aged 50 to 70 years
• AMS score = 27
• IIEF < 14
• SQoL-M = 87
• and Testosterone = 12 nMol/L
• Normal liver function (ALT, AST and Bilirubin are normal according to biological index of Vietnamese people).
• Normal kidney function is usually according to the biological index of Vietnamese people.
• No infection, HIV, HBV, active syphilis.
• Must provide written informed consent.

Exclusion Criteria:

• The patient had surgery to remove the gonads.
• Patients with a history of cancer, or undergoing cancer treatment, or are positive for cancer screening tests including: PSA, AFP, Pepsinogen I, Pepsinogen II and erythrocyte smear test. The patient is taking anti-rejection drugs.
• Patients with malformations, malformations or tumors of the endocrine glands.
• Endocrine impairment due to diabetes (HBA1c > 7) and other metabolic diseases.
• Patients with active autoimmune disease or positive for antinuclear antibodies.
• Patients with severe heart failure, severe renal failure, severe liver failure, severe respiratory failure, history of cerebral infarction, myocardial infarction, Alzeimer.
• Patients with hypothyroidism.
• The patient has an acute infection.
• Patients with clinically significant coagulopathy or other hematological diseases.
• History of allergy to anesthetics, anesthetics, antibiotics.
• Patients who are using other hormone-improving drugs or supplements (including Sildenafil) in the last 2 weeks or want to continue using these drugs during the study period.
• The patient is a smoker.

Related Conditions & MeSH terms

• Sexual Dysfunction Male

Intervention

Biological:
• Umbilical Cord-Derived Mesenchymal Stem Cell for Male Patients with Sexual Deficiency
Patients will receive two administrations at a dose of 1.5 million cells/kg patient bodyweight via the IV route with a 3-month intervening interval. A validated umbilical cord blood mesenchymal stem cells (UC-MSC) line was selected from the Vinmec Tissue Bank and cultured under xeno-free, serum-free and antibiotic-free conditions as previously described. To prepare UC-MSCs for therapy, aliquots of Passage 3 (P3) UC-MSCs will be thawed and cultured to P5 to get approximately 500 million cells and dispensed to 10 million UC-MSCs/ml/vial for cryopreservation. Upon request from the clinical team, aliquots of P5 UC-MSCs will be thawed in a temperature control water bath or incubator on the infusion day. The UC-MSCs will be washed and suspended in Ringer Lactate.

Locations

Country	Name	City	State
Vietnam	Vinmec Research Institute of Stem Cell and Gene Technology	Hanoi

Sponsors (1)

Lead Sponsor	Collaborator
Vinmec Research Institute of Stem Cell and Gene Technology

Country where clinical trial is conducted

Vietnam, 

References & Publications (3)

Kadihasanoglu M, Ozbek E. Mesenchymal stem cell therapy in treatment of erectile dysfunction: Autologous or allogeneic cell sources? Int J Urol. 2016 Apr;23(4):348-9. doi: 10.1111/iju.13058. Epub 2016 Jan 28. — View Citation

Kouchakian MR, Baghban N, Moniri SF, Baghban M, Bakhshalizadeh S, Najafzadeh V, Safaei Z, Izanlou S, Khoradmehr A, Nabipour I, Shirazi R, Tamadon A. The Clinical Trials of Mesenchymal Stromal Cells Therapy. Stem Cells Int. 2021 Nov 3;2021:1634782. doi: 10.1155/2021/1634782. eCollection 2021. Review. — View Citation

Zhang ZY, Xing XY, Ju GQ, Zhong L, Sun J. Mesenchymal stem cells from human umbilical cord ameliorate testicular dysfunction in a male rat hypogonadism model. Asian J Androl. 2017 Sep-Oct;19(5):543-547. doi: 10.4103/1008-682X.186186. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The safety of allogenic umbilical cord-derived mesenchymal stem cell administration for the treatment of hormone deficiency in male	To assess safety, the number of AEs or SAEs during stem cell administration up to the 12-month period following treatment will be evaluated	up to the 12-month period following treatment
Primary	Testosterone levels	To evaluate the Testosterone levels of the patients with sexual functional deficiency	up to the 12-month period following treatment
Primary	Changes in sexual life quality using Aging Men Symptom (AMS)	AMS includes 10 items	up to the 12-month period following treatment
Primary	Changes in sexual life quality through quantification of International Index of Erectile Function (IIEF)	IIEF includes 15 items	up to the 12-month period following treatment
Primary	Changes in sexual life quality through quantification of Sexual Quality of Life Questionnaire (SQoL-M)	IIEF includes 11 items	up to the 12-month period following treatment