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Male InfertilityPhase 2RA-2NCT02061384

RA-2 13-cis Retinoic Acid (Isotretinoin)

A Phase 2 study testing 13-cis retinoic acid and Calcitriol in people with Male Infertility and Klinefelter's Syndrome, run by University of Washington at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Men with infertility and normal hormone levels have few options for fertility treatment. Previous research work has suggested that men with infertility may have low levels of the active form of Vitamin A, called retinoic acid, in their testes. Read more about this study

Who is it for?
Ages 21 to 60 years, men only
What is being tested?
13-cis retinoic acid and Calcitriol
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
Aug 2014to Dec 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 21 to 60 years
  • Men only
  • No healthy volunteers
  • Adult

Who may be able to join

  • Subjects will be infertile men (no pregnancy with partner with normal cycles and normal hysterosalpingogram despite >1 year of unprotected intercourse).
  • Abnormal sperm analyses with a total, motile sperm count of less than 10 million sperm as assessed by semen analysis on two occasions separated by one week.
  • In the opinion of the investigator, is able to comply with the protocol, understand and sign an informed consent and HIPAA (Health Insurance Portability and Accountability Act ) form.

Who cannot join

  • Men participating in another clinical trial
  • Men not living in the catchment area of the clinic
  • Clinically significant abnormal findings at screening
  • Known genetic infertility (e.g. Klinefelter syndrome or Y-chromosome microdeletions),
  • Hypogonadotropic hypogonadism (that might respond to gonadotropin injections),
  • The use of anabolic steroids, illicit drugs, or the consumption of more than 4 alcoholic beverages daily
Show all 17Show fewer
  • Severe mental health problems requiring medications
  • Current therapy with retinoic acid (e.g. Accutane) or vitamin A.
  • Score of greater than 15 on the Patient health questionnaire (PHQ9).
  • Abnormal serum chemistry values according to local laboratory normal values which indicate liver or kidney dysfunction. Other abnormal lab values may also be exclusionary, at the discretion of the investigator
  • Men with a personal history of serious psychiatric disorders
  • Men currently receiving tetracycline containing medications
  • Men currently receiving phenytoin
  • Men with a history of inflammatory bowel disease
  • Men with a history of bone disease
  • Men who have used isotretinoin within eight weeks of the start of dosing
  • Men with elevated serum triglycerides

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Washington Medical Center

    Seattle, Washington, 98195

Other trials in United States

About this study

Official title: A Pilot Trial of 13-cis Retinoic Acid (Isotretinoin) for the Treatment of Men With Oligoasthenoteratozoospermia

Men with infertility and normal hormone levels have few options for fertility treatment. Previous research work has suggested that men with infertility may have low levels of the active form of Vitamin A, called retinoic acid, in their testes. We think that giving men with low sperm counts retinoic acid may increase their sperm counts and improve their chances of fathering a pregnancy. We want to see if retinoic acid administration over twenty weeks can increase sperm production and help infertile men become fathers without the need for In vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI). We also want to see if adding calcitriol with retinoic acid will improve sperm motility in a sub-set of subjects.

Read the detailed description

This is a 20 week, unblinded, two-arm pilot study to determine the impact of therapy with 13-cis retinoic acid and calcitriol on sperm indices in infertile men. Twenty infertile men, ages 21-60 with abnormal sperm analyses will be enrolled for 20-week and given 20 mg 13-cis retinoic acid, twice daily. Subjects#11-#20 will also be administered calcitriol to see if adding calcitriol with Accutane will improve sperm motility. All subjects will be closely followed for side effects related to treatment. The impact of treatment on indices of spermatogenesis will be determined by monthly seminal fluid analyses.

Being tested
13-cis retinoic acid, Calcitriol
Keywords
Infertility
Medical subject headings
Infertility, Male, Klinefelter Syndrome, Male sterility due to Y-chromosome deletions, Infertility

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 13-cis retinoic acidDrug

    Also called Accutane, Isotretinoin

    Accutane is used for the treatment of severe acne

  • CalcitriolDrug

    Also called 1,25-dihydroxyvitamin D3

    Calcitriol is a form of vitamin D given twice daily (BID)

Study groups in NCT02061384
Study groupRoleWhat they receive
13-cis retinoic acidExperimental20mg 13-cis retinoic acid twice daily (BID) with meals for 20 weeks
Receives: Drug: 13-cis retinoic acid
Calcitriol 0.25 mcgExperimentaloral calcitriol 025 mcg BID subjects 11-20 for 20 weeks
Receives: Drug: 13-cis retinoic acid; Drug: Calcitriol

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Millions of Sperm Per Ejaculate

    Millions of sperm per ejaculate in men treated with 13-cis retinoic acid

    Measured: Up to 20-weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Feb 2014 (estimated)
  2. Study startAug 2014
  3. Primary completionDec 2018
  4. Study completionDec 2018

Resources

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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02061384
Sponsor's protocol ID
STUDY00000564
Acronym
RA-2
Status last verified
Jun 2021
First submitted
10 Feb 2014
Last updated
2 Aug 2021
Data monitoring committee
No

Publications

  • Jequier AM, Holmes SC. Primary testicular disease presenting as azoospermia or oligozoospermia in an infertility clinic. Br J Urol. 1993 Jun;71(6):731-5. doi: 10.1111/j.1464-410x.1993.tb16075.x.

    PubMed 8102079

  • de Kretser DM. Male infertility. Lancet. 1997 Mar 15;349(9054):787-90. doi: 10.1016/s0140-6736(96)08341-9. No abstract available.

    PubMed 9074589

  • Schlegel PN. Nonobstructive azoospermia: a revolutionary surgical approach and results. Semin Reprod Med. 2009 Mar;27(2):165-70. doi: 10.1055/s-0029-1202305. Epub 2009 Feb 26.

    PubMed 19247918

  • Napoli JL. Retinoic acid: its biosynthesis and metabolism. Prog Nucleic Acid Res Mol Biol. 1999;63:139-88. doi: 10.1016/s0079-6603(08)60722-9.

    PubMed 10506831

  • Center for Disease Control. Infertility Facts,m accessed at http://www.ede.gov/nchs/fastats/fertile.htm (June 3, 2013)

  • Doyle TJ, Braun KW, McLean DJ, Wright RW, Griswold MD, Kim KH. Potential functions of retinoic acid receptor A in Sertoli cells and germ cells during spermatogenesis. Ann N Y Acad Sci. 2007 Dec;1120:114-30. doi: 10.1196/annals.1411.008. Epub 2007 Sep 28.

    PubMed 17905941

  • Koubova J, Menke DB, Zhou Q, Capel B, Griswold MD, Page DC. Retinoic acid regulates sex-specific timing of meiotic initiation in mice. Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2474-9. doi: 10.1073/pnas.0510813103. Epub 2006 Feb 6.

    PubMed 16461896

  • Anderson EL, Baltus AE, Roepers-Gajadien HL, Hassold TJ, de Rooij DG, van Pelt AM, Page DC. Stra8 and its inducer, retinoic acid, regulate meiotic initiation in both spermatogenesis and oogenesis in mice. Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):14976-80. doi: 10.1073/pnas.0807297105. Epub 2008 Sep 17.

    PubMed 18799751

  • Chung SS, Wang X, Wolgemuth DJ. Expression of retinoic acid receptor alpha in the germline is essential for proper cellular association and spermiogenesis during spermatogenesis. Development. 2009 Jun;136(12):2091-100. doi: 10.1242/dev.020040.

    PubMed 19465599

  • Dufour JM, Kim KH. Cellular and subcellular localization of six retinoid receptors in rat testis during postnatal development: identification of potential heterodimeric receptors. Biol Reprod. 1999 Nov;61(5):1300-8. doi: 10.1095/biolreprod61.5.1300.

    PubMed 10529278

  • Lohnes D, Kastner P, Dierich A, Mark M, LeMeur M, Chambon P. Function of retinoic acid receptor gamma in the mouse. Cell. 1993 May 21;73(4):643-58. doi: 10.1016/0092-8674(93)90246-m.

    PubMed 8388780

  • Lufkin T, Lohnes D, Mark M, Dierich A, Gorry P, Gaub MP, LeMeur M, Chambon P. High postnatal lethality and testis degeneration in retinoic acid receptor alpha mutant mice. Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7225-9. doi: 10.1073/pnas.90.15.7225.

    PubMed 8394014

  • Kastner P, Mark M, Leid M, Gansmuller A, Chin W, Grondona JM, Decimo D, Krezel W, Dierich A, Chambon P. Abnormal spermatogenesis in RXR beta mutant mice. Genes Dev. 1996 Jan 1;10(1):80-92. doi: 10.1101/gad.10.1.80.

    PubMed 8557197

  • Ghyselinck NB, Vernet N, Dennefeld C, Giese N, Nau H, Chambon P, Viville S, Mark M. Retinoids and spermatogenesis: lessons from mutant mice lacking the plasma retinol binding protein. Dev Dyn. 2006 Jun;235(6):1608-22. doi: 10.1002/dvdy.20795.

    PubMed 16586441

  • Hoting VE, Schutte B, Schirren C. [Isotretinoin treatment of acne conglobata. Andrologic follow-up]. Fortschr Med. 1992 Aug 20;110(23):427-30. German.

    PubMed 1398387

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing 13-cis retinoic acid and Calcitriol in people with Male Infertility and Klinefelter's Syndrome, run by University of Washington at 1 site in United States.

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 3 inclusion and 17 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 2 Aug 2021. 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 United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Millions of Sperm Per Ejaculate (time frame: Up to 20-weeks). 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 NCT02061384, which also lists 25 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 2 Aug 2021.

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