Effects of Telomerase Reactivation With Danazol in Ovarian Function.

NCT04058678 | Completed DMC

• 1 other identifier: 1707-FIVI-084-MV
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

This project explores the implication of the telomere pathway in ovarian premature and regular aging. Telomere length and maintenance underlie several biological processes such cancer, aging, human diseases and the biology of stem cells. The reactivation of telomerase should lead to a rejuvenation of the ovarian tissue and the improvement of fertility. The correlation of telomeric factors in blood and granulosa cells will be studied with the aim of finding telomeric biomarkers of ovarian aging.

Conditions

Ovarian Reserve

Keywords

Ovarian reserve.; Telomeric factor; Blood; Granulosa cells

Outcome Measures

Primary Outcomes (1)

• Telomere length in granulosa cells

  Measured in arbitrary units of fluorescence (a.u.) from 0 to 255 gray intensity (8bit) or Kb (continuous variable). Below 3 kb are considered critically short telomeres in humans.

  The evaluation of the main assessment criterion will be done both after eighth visit (36 hours post induction) for women with low ovarian reserve and fifth visit for woman with normal ovarian reserve

Secondary Outcomes (4)

• Accumulation of short telomeres

  Through study completion, an average of 1 year

• Telomerase activity

  Through study completion, an average of 1 year

• DNA damage measurement

  Through study completion, an average of 1 year

• Other telomeric factors.

  Through study completion, an average of 1 year

Study Arms (2)

CONTROL

SHAM COMPARATOR

A control group composed of women with normal ovarian reserve (30 to 45 yerras old) is needed to compare telomeric and fertility parameters with the group of women with compromised ovarian reserve. Note that the term "normal ovarian reserve" referred to older women indicates women that still have follicles in their ovaries -and thus, normal AMH values-, even though the number may be lower tan at a younger age or the quality of oocytes may be lower tan in younger women. In other words, women in the control group irrespective of their age, will have a greater number of follicles compared to women belonging to the group with compromised ovarian reserve.

Other: Without intervention

EXPERIMENTAL

EXPERIMENTAL

A group of women with diminished ovarian reserve that will take an inactive substance has been included to avoik biases and to set the fertility base line for women with compromised ovarian reserve.

Drug: Danazol/Placebo

Interventions

Danazol/Placebo DRUG

This group will be randomized 1:1 for either inactive substance or Danazol, according to a computer-generated randomization list prepared. Women will be treated with Danazol/Placebo oral way for 3 months.

EXPERIMENTAL

Without intervention OTHER

Women with normal ovarian reserve will not be treated in anyway, thus, randomization will not be necessary.

CONTROL

Eligibility Criteria

• Age: 30 Years - 45 Years
• Gender Eligibility Details: Most frequent population of women seeking for ART
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Provide signed and dated informed consent form.
• Willing to comply with all study procedures and be available for the duration of the study. This include the decisión to use contraception methods different to sexual hormones, such as the use of condoms, during the treatment with Danazol.
• In good general health as evidenced by medical history or diagnosed with body mass index between 18 and 30 kg/m2.
• Women with normal (AMH valued must be equal or higher tan 2ng/ml) or compromised ovarian reserve (defined as AMH \< 2 ng/ml)
• Not having had any steroid hormones for one month.

You may not qualify if:

• Pregnancy o lactation.
• Taking other sexual hormones.
• Women with diseases in heart, liver or kidney or tumors which depend on male sexual hormones or hormone-dependent tumour.
• Women taking anticonvulsants, medicaments for diabetes, anticoagulants and anti-hypertension: ciclosporin and tacrolimus and other steroids and statins.
• Women suffering irregular genital bleeding or with thrombus or thromboembolicdiseases.
• Known allergic reactions to components of the study product (cornstarch and lactose).
• Having received ovulation induction drugs within one month before the inclusión in the study.
• Anything that would place the individual at increased risk or preclude the individual´s full compliance with or completion of the study.
• Simultaneous participation in another clinical trial or previous participation in this study.
• Participation in another clinical study 2 months before inclusión in the present study that could affect its objectives.

Sponsors & Collaborators

• IVI Madrid: lead

Study Sites (1)

Ivirma Madrid

Madrid, 28023, Spain

Location

Related Publications (4)

• Armanios MY, Chen JJ, Cogan JD, Alder JK, Ingersoll RG, Markin C, Lawson WE, Xie M, Vulto I, Phillips JA 3rd, Lansdorp PM, Greider CW, Loyd JE. Telomerase mutations in families with idiopathic pulmonary fibrosis. N Engl J Med. 2007 Mar 29;356(13):1317-26. doi: 10.1056/NEJMoa066157.

  PMID: 17392301 BACKGROUND

• Blasco MA, Lee HW, Hande MP, Samper E, Lansdorp PM, DePinho RA, Greider CW. Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell. 1997 Oct 3;91(1):25-34. doi: 10.1016/s0092-8674(01)80006-4.

  PMID: 9335332 BACKGROUND

• Blasco MA. Telomeres and human disease: ageing, cancer and beyond. Nat Rev Genet. 2005 Aug;6(8):611-22. doi: 10.1038/nrg1656.

  PMID: 16136653 BACKGROUND

• Bernardes de Jesus B, Vera E, Schneeberger K, Tejera AM, Ayuso E, Bosch F, Blasco MA. Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer. EMBO Mol Med. 2012 Aug;4(8):691-704. doi: 10.1002/emmm.201200245. Epub 2012 May 15.

  PMID: 22585399 BACKGROUND

MeSH Terms

Interventions

Danazol; Methods

Intervention Hierarchy (Ancestors)

Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Investigative Techniques

Study Officials

• María Elisa Varela

  IVIRMA MADRID

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: During the first visist to the doctor, women will be selected according to the selection criteria. Those who seem to have a low ovarian reserve by ultrasound will be informed of the trial, and if they decide to participate, blood will be taken to analyze AMH values. On the second visit, women with low ovarian reserve will be randomized 1:1 for either inactive substance or Danazo, accordint to a computer-generated randomization list prepared by associated statistic. This way, the assigned group will be blind until the momento of executing the randomization procedure. Moment in which, the assigned group will be revealed. Those with normal ovarian reserve will not be randomized and will just be included as controls. To maintain the blinding of the trial, Danazol and placebo will be provided in boxs with blisters (PVC opaque and aluminium sealed). Only the trial medication delegate(s) at the site will dispense the IMP and will know the treatment allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD in Medicine and gynecology, University professor

Model Details: A control group composed of women with normal ovarian reserve to compare telomeric and fertility parameters with the group with compromised ovarian reserve.

Study Record Dates

• First Submitted: August 12, 2019
• First Posted: August 15, 2019
• Study Start: January 30, 2020
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: August 10, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)