Ovarian ReserveNCT04058678
Effects of Telomerase Reactivation With Danazol in Ovarian Function.
A study testing Without intervention in people with Ovarian Reserve, run by IVI Madrid at 1 site in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 to 45 years, women only
- Conditions the study is for
- Ovarian Reserve
- What is being tested?
- Without intervention
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 19 participants
- Where
- 1 siteSpain
- Study dates
- 30 Jan 2020to 31 Dec 2021
- Phase
- Interventional
- 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 30 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
This is a pilot study, randomized, controled, blind, parallelo arm clinical trial with inactive substance and medicine.
A pilot study will be developed with a total of 45 individuals from 30 to 45 years old, who represent the most frequent population of women seeking for ART.
A control group composed of women with normal ovarian reserve (30 to 45 years old) is needed to compare telomeric and fertility parameters with the group of women with compromised ovarian reserve. 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.
A group of women with diminished ovarian reserve that will take an inactive substance has been incluided to avoid biases and to set the fertility base line for women with compromised ovarian reserve. The use of an inactive substance or placebo will help obtain better quality results. For instance, if Danazol happened to improve the fertility outcome, then, there could be a possibility that the IVF improvement might be due to other components of the pill. Using placebo, this possibility would be eliminated, since the placebo will contain all components of the pill, except Danazol.
The development of a pilot study will help us understand the statisticl behavior or the telomeric factors as well as to determine the appropriate number of individuals that shoyuld be recruited in a clinical trial to have results with statistical significance. In addition, a pilot study will help us learn errors or undesired events that may happen during the clinical trial. For instance, if patients cannot follow the indications of their doctors and why, or what proportion of patients will drop the study and the reasons for it. Furthermore, it will also help us understand if there exist a tendency, an indication or even a clear beneficial effect for patients without harming them.
The number of participants selected for the study is considered adequate for each group, since each group will be measured in an independent manner.
- Conditions
- Ovarian Reserve
- Being tested
- Danazol/Placebo, Without intervention
- Keywords
- Ovarian reserve., Telomeric factor, Blood, Granulosa cells
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Danazol/PlaceboDrug
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.
Without interventionOther
Women with normal ovarian reserve will not be treated in anyway, thus, randomization will not be necessary.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Danazol/Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: Through study completion, an average of 1 year
Telomerase activity
Product of PCR amplification, run in acrylamide gels and quantified as band intensity (continuous variable)
Measured: Through study completion, an average of 1 year
DNA damage measurement
If damage is positive, then different foci should be apparent in the nucleus of the cell. The number of foci present in the nuclei of at least 100 cells will be counted. If there is DNA damage at telomeres, then yH2AX or 53BPI foci will colocalize with telomeres (labelled with anti TRF1 antibody). Spots will be counted (continuous variable).
Measured: Through study completion, an average of 1 year
Other telomeric factors.
The mRNA expression levels of the telomerase gene and the shelterins, which are involved in telomere lengthening and protection, will be measured by qPCR. (continuous variable).
Measured: Through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2019
- Study start30 Jan 2020
- Primary completion31 Dec 2021
- Study completion31 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Ovarian ReserveStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A control group composed of women with normal ovarian reserve to compare telomeric and fertility parameters with the group with compromised ovarian reserve.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- IVI Madrid
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Juan A Garcia-Velasco, IVI Madrid
- Investigators
- María Elisa Varela, Principal investigator, IVIRMA MADRID
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04058678
- Sponsor's protocol ID
- 1707-FIVI-084-MV
- Status last verified
- Aug 2022
- First submitted
- 12 Aug 2019
- Last updated
- 10 Aug 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 17392301Blasco 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.
PubMed 9335332Blasco MA. Telomeres and human disease: ageing, cancer and beyond. Nat Rev Genet. 2005 Aug;6(8):611-22. doi: 10.1038/nrg1656.
PubMed 16136653Bernardes 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.
PubMed 22585399
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Telomerase Reactivation With Danazol in Ovarian Function.
- ClinicalTrials.gov ID
- NCT04058678
- Acronym / sponsor ID
- 1707-FIVI-084-MV
- Conditions
- Ovarian Reserve
- Keywords
- Ovarian reserve., Telomeric factor, Blood, Granulosa cells
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- IVI MadridUniversity, hospital or other
- Study start
- 30 Jan 2020 (actual)
- Primary completion
- 31 Dec 2021 (actual)
- Study completion
- 31 Dec 2021 (actual)
- First posted
- 15 Aug 2019 (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 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.
Detailed description
This is a pilot study, randomized, controled, blind, parallelo arm clinical trial with inactive substance and medicine.
A pilot study will be developed with a total of 45 individuals from 30 to 45 years old, who represent the most frequent population of women seeking for ART.
A control group composed of women with normal ovarian reserve (30 to 45 years old) is needed to compare telomeric and fertility parameters with the group of women with compromised ovarian reserve. 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.
A group of women with diminished ovarian reserve that will take an inactive substance has been incluided to avoid biases and to set the fertility base line for women with compromised ovarian reserve. The use of an inactive substance or placebo will help obtain better quality results. For instance, if Danazol happened to improve the fertility outcome, then, there could be a possibility that the IVF improvement might be due to other components of the pill. Using placebo, this possibility would be eliminated, since the placebo will contain all components of the pill, except Danazol.
The development of a pilot study will help us understand the statisticl behavior or the telomeric factors as well as to determine the appropriate number of individuals that shoyuld be recruited in a clinical trial to have results with statistical significance. In addition, a pilot study will help us learn errors or undesired events that may happen during the clinical trial. For instance, if patients cannot follow the indications of their doctors and why, or what proportion of patients will drop the study and the reasons for it. Furthermore, it will also help us understand if there exist a tendency, an indication or even a clear beneficial effect for patients without harming them.
The number of participants selected for the study is considered adequate for each group, since each group will be measured in an independent manner.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- A control group composed of women with normal ovarian reserve to compare telomeric and fertility parameters with the group with compromised ovarian reserve.
| Arm | Type | Receives |
|---|---|---|
| CONTROL | Sham comparator | Other: Without interventionA 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. |
| EXPERIMENTAL | Experimental | Drug: Danazol/PlaceboA 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. |
Who may qualify
- Ages
- 30 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
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 |
|---|---|---|
| Danazol/PlaceboThis 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. | Drug | EXPERIMENTAL |
| Without interventionWomen with normal ovarian reserve will not be treated in anyway, thus, randomization will not be necessary. | Other | CONTROL |
Primary outcome
Telomere length in granulosa cells
Time frame: 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
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.
4 secondary outcomes
Accumulation of short telomeres
Time frame: Through study completion, an average of 1 year
Telomerase activity
Time frame: Through study completion, an average of 1 year
DNA damage measurement
Time frame: Through study completion, an average of 1 year
Other telomeric factors.
Time frame: Through study completion, an average of 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2022.
- Background: PubMed 17392301Armanios 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.
- Background: PubMed 9335332Blasco 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.
- Background: PubMed 16136653Blasco MA. Telomeres and human disease: ageing, cancer and beyond. Nat Rev Genet. 2005 Aug;6(8):611-22. doi: 10.1038/nrg1656.
- Background: PubMed 22585399Bernardes 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.
- 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.
María Elisa Varela principal investigator
IVIRMA MADRID
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Without intervention in people with Ovarian Reserve, run by IVI Madrid at 1 site in Spain.
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 5 inclusion and 10 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: finished, as of the sponsor's last update on 10 Aug 2022. 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 Spain. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Telomere length in granulosa cells (time frame: 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). 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 NCT04058678, which also lists 4 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 10 Aug 2022.