Kallmann SyndromeNCT01601171
Genetics of Reproductive Disorders (Including Kallmann Syndrome) and Cleft Lip and/or Palate
An observational study of Kallmann Syndrome and Hypogonadotropic Hypogonadism, run by Centre Hospitalier Universitaire Vaudois at 1 site in Switzerland.
Trial summary
The purpose of this study is to explore the genetic basis of reproductive disorders and cleft lip and/or palate. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Kallmann Syndrome, Hypogonadotropic Hypogonadism, Hypothalamic Amenorrhea
- How many people
- 2,000 participants
- Where
- 1 siteSwitzerland
- Study dates
- Mar 2012to Mar 2030
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Study participants will be a convenience sample of those patients with reproductive disorders (and their family members), with or without cleft lip/palate, who are interested in participating in this genetic study.
Who may be able to join
- hypogonadotropic hypogonadism
- Kallmann syndrome
- adult-onset hypogonadotropic hypogonadism
- hypothalamic amenorrhea
- polycystic ovarian syndrome
- primary gonadal failure
Show all 9Show fewer
- precocious puberty
- cleft lip/palate
- family members of the above groups
Who cannot join
- acute illness/hospitalization
- pituitary tumors
- iron overload (hemochromatosis)
- infiltrative diseases (sarcoidosis)
- chronic alcohol abuse
- illicit drug use
- anabolic steroid abuse
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Switzerland1 site, 1 recruiting
- Recruiting
Centre Hospitalier Universitaire Vaudois (CHUV)
Lausanne, Canton of Vaud, 1011
Emmanuelle Paccou, +41 79 556 60 13, emmanuelle.paccou@chuv.ch
Michela Adamo, MD, +41 079 556 85 14, michela.adamo@chuv.ch
About this study
Official title: The Genetics of Neuroendocrine Reproductive Disorders and of the Cleft Lip and/or Palate
The purpose of this study is to explore the genetic basis of reproductive disorders and cleft lip and/or palate.
Read the detailed description
The World Health Organization estimates approximately 10% of couples experience some sort of infertility problem.
In humans, puberty is the process through which we develop reproductive capacity.
The timing of puberty varies greatly in the general population and is influenced by both genetic and environmental factors. In extreme cases of pubertal delay, puberty progresses only partially or not at all and results in the clinical picture of congenital hypogonadotropic hypogonadism (CHH), either accompanied by anosmia in 50% of cases (Kallmann syndrome [KS]) or by normal sense of smell (nCHH), with a male: female ratio of 4:1.
CHH is due to GnRH deficiency (incidence 1: 4,000-10,000) and result in the failure of sexual maturation and infertility. It is genetically heterogeneous, with multiple patterns of inheritance and several associated loci. In the clinical spectrum of GnRH deficiency, CHH may also be associated with a cleft lip/palate (CL/P) in 5 to 7% of cases. However, this prevalence increases up to 40% in CHH patients carrying a mutation in a CL/P gene, suggesting a genetic overlap between CHH and CL/P.
Disorders of puberty have provided insight into the biology of reproduction and genetic technologies have enabled us to deepen understanding in this field. The focus of this study is to better understand the genetic control of puberty and human reproduction as well as its link with CL/P.
Increasing understanding of the molecular basis (genes) of inherited reproductive disorders and CL/P may enable investigators to:
- improve diagnostic testing and treatments for these problems
- develop new diagnostic tests and therapies for patients
- enhance counseling for patients and families with reproductive disorders
- enhance counseling for patients and families with cleft lip/palate
- Conditions
- Kallmann Syndrome, Hypogonadotropic Hypogonadism, Hypothalamic Amenorrhea, Polycystic Ovarian Syndrome, Precocious Puberty, Cleft Lip and Palate
- Keywords
- GnRH deficiency, hypogonadism, anosmia, infertility, cleft lip, cleft palate, cryptorchidism, microphallus
- Medical subject headings
- Kallmann Syndrome, Hypogonadism, Polycystic Ovary Syndrome, Puberty, Precocious, Cleft Lip, Cleft Palate, Anosmia, Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Patients | Patients with reproductive disorders with or without cleft lip/palate will be recruited for: * completion of medical questionnaire and review of medical records * family tree (including questions on reproductive disorders and cleft lip/palate) * specimen collection (DNA/RNA) from: serum/plasma/saliva/urine/buccal swab/hair follicles/sperm/skin biopsy * smell testing * hearing test * bone density * brain MRI * kidney, testicular/ovarian ultrasound | |
| Family members | Family members of Patients will be recruited for: * completion of medical questionnaire * specimen collection (DNA/RNA) from: serum/plasma/saliva/urine/buccal swab/hair follicles/sperm/skin biopsy * smell testing |
What is being measured
The primary outcome is the main question the study is designed to answer.
rare sequence variant(s) in gene(s)
The investigators aim to discover genes associated with reproductive disorders by identifying rare sequence variants (mutations) in patients
Measured: 1 year (ongoing if no variants are identified)
Secondary outcomes (3)
functionality of identified rare sequence variants (mutations)
The investigators will use a variety of scientific approaches to assess the functional impact of the identified rare sequence variants (mutations)
Measured: 1 year (following variant identification)
mode of inheritance
The investigators will examine family pedigrees and study family members to determine the inheritance patterns (how the disorder is transmitted in the family)
Measured: 1 year (following variant identification)
genotype-phenotype correlation
The investigators will study the phenotypic spectrum (how the disorder presents clinically) in patients with identified rare sequence variants (mutations)
Measured: 1 year (following variant identification)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2012 (estimated)
- Study startMar 2012
- Primary completionMar 2025 (estimated)
- Study completionMar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Kallmann SyndromeStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire VaudoisThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Case-control
- Time perspective
- Other
- Enrolment
- 2,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire Vaudois
- Sponsor type
- University, hospital or other
- Collaborators
- Swiss National Science Foundation
- Responsible party
- Principal investigator, Nelly Pitteloud, Centre Hospitalier Universitaire Vaudois
- Investigators
- Nelly Pitteloud, M.D., Principal investigator, Centre Hositalier Universitaire Vaudois (CHUV)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01601171
- Sponsor's protocol ID
- 345/11
- Status last verified
- Jun 2022
- First submitted
- 15 May 2012
- Last updated
- 21 Jun 2022
- Results posted
- No
- Data monitoring committee
- No
Publications
Miraoui H, Dwyer AA, Sykiotis GP, Plummer L, Chung W, Feng B, Beenken A, Clarke J, Pers TH, Dworzynski P, Keefe K, Niedziela M, Raivio T, Crowley WF Jr, Seminara SB, Quinton R, Hughes VA, Kumanov P, Young J, Yialamas MA, Hall JE, Van Vliet G, Chanoine JP, Rubenstein J, Mohammadi M, Tsai PS, Sidis Y, Lage K, Pitteloud N. Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism. Am J Hum Genet. 2013 May 2;92(5):725-43. doi: 10.1016/j.ajhg.2013.04.008.
PubMed 23643382Villanueva C, Jacobson-Dickman E, Xu C, Manouvrier S, Dwyer AA, Sykiotis GP, Beenken A, Liu Y, Tommiska J, Hu Y, Tiosano D, Gerard M, Leger J, Drouin-Garraud V, Lefebvre H, Polak M, Carel JC, Phan-Hug F, Hauschild M, Plummer L, Rey JP, Raivio T, Bouloux P, Sidis Y, Mohammadi M, de Roux N, Pitteloud N. Congenital hypogonadotropic hypogonadism with split hand/foot malformation: a clinical entity with a high frequency of FGFR1 mutations. Genet Med. 2015 Aug;17(8):651-9. doi: 10.1038/gim.2014.166. Epub 2014 Nov 13.
PubMed 25394172
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Genetics of Neuroendocrine Reproductive Disorders and of the Cleft Lip and/or Palate
- ClinicalTrials.gov ID
- NCT01601171
- Acronym / sponsor ID
- 345/11
- Conditions
- Kallmann Syndrome, Hypogonadotropic Hypogonadism, Hypothalamic Amenorrhea, Polycystic Ovarian Syndrome, Precocious Puberty, Cleft Lip and Palate
- Keywords
- GnRH deficiency, hypogonadism, anosmia, infertility, cleft lip, cleft palate, cryptorchidism, microphallus
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 2,000 participants (estimated)
- Lead sponsor
- Centre Hospitalier Universitaire VaudoisUniversity, hospital or other
- Collaborators
- Swiss National Science Foundation
- Study start
- Mar 2012
- Primary completion
- Mar 2025 (estimated)
- Study completion
- Mar 2030 (estimated)
- First posted
- 17 May 2012 (estimated)
- 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.
The purpose of this study is to explore the genetic basis of reproductive disorders and cleft lip and/or palate.
Detailed description
The World Health Organization estimates approximately 10% of couples experience some sort of infertility problem.
In humans, puberty is the process through which we develop reproductive capacity.
The timing of puberty varies greatly in the general population and is influenced by both genetic and environmental factors. In extreme cases of pubertal delay, puberty progresses only partially or not at all and results in the clinical picture of congenital hypogonadotropic hypogonadism (CHH), either accompanied by anosmia in 50% of cases (Kallmann syndrome [KS]) or by normal sense of smell (nCHH), with a male: female ratio of 4:1.
CHH is due to GnRH deficiency (incidence 1: 4,000-10,000) and result in the failure of sexual maturation and infertility. It is genetically heterogeneous, with multiple patterns of inheritance and several associated loci. In the clinical spectrum of GnRH deficiency, CHH may also be associated with a cleft lip/palate (CL/P) in 5 to 7% of cases. However, this prevalence increases up to 40% in CHH patients carrying a mutation in a CL/P gene, suggesting a genetic overlap between CHH and CL/P.
Disorders of puberty have provided insight into the biology of reproduction and genetic technologies have enabled us to deepen understanding in this field. The focus of this study is to better understand the genetic control of puberty and human reproduction as well as its link with CL/P.
Increasing understanding of the molecular basis (genes) of inherited reproductive disorders and CL/P may enable investigators to:
- improve diagnostic testing and treatments for these problems
- develop new diagnostic tests and therapies for patients
- enhance counseling for patients and families with reproductive disorders
- enhance counseling for patients and families with cleft lip/palate
Study design
- Observational model
- Case-control
- Time perspective
- Other
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients | – | –Patients with reproductive disorders with or without cleft lip/palate will be recruited for: * completion of medical questionnaire and review of medical records * family tree (including questions on reproductive disorders and cleft lip/palate) * specimen collection (DNA/RNA) from: serum/plasma/saliva/urine/buccal swab/hair follicles/sperm/skin biopsy * smell testing * hearing test * bone density * brain MRI * kidney, testicular/ovarian ultrasound |
| Family members | – | –Family members of Patients will be recruited for: * completion of medical questionnaire * specimen collection (DNA/RNA) from: serum/plasma/saliva/urine/buccal swab/hair follicles/sperm/skin biopsy * smell testing |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Study participants will be a convenience sample of those patients with reproductive disorders (and their family members), with or without cleft lip/palate, who are interested in participating in this genetic study.
Key inclusion criteria (9 listed)
- hypogonadotropic hypogonadism
- Kallmann syndrome
- adult-onset hypogonadotropic hypogonadism
- hypothalamic amenorrhea
- polycystic ovarian syndrome
Key exclusion criteria (7 listed)
- acute illness/hospitalization
- pituitary tumors
- iron overload (hemochromatosis)
- infiltrative diseases (sarcoidosis)
- chronic alcohol abuse
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
rare sequence variant(s) in gene(s)
Time frame: 1 year (ongoing if no variants are identified)
The investigators aim to discover genes associated with reproductive disorders by identifying rare sequence variants (mutations) in patients
3 secondary outcomes
functionality of identified rare sequence variants (mutations)
Time frame: 1 year (following variant identification)
mode of inheritance
Time frame: 1 year (following variant identification)
genotype-phenotype correlation
Time frame: 1 year (following variant identification)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2022.
- Results publication: PubMed 23643382Miraoui H, Dwyer AA, Sykiotis GP, Plummer L, Chung W, Feng B, Beenken A, Clarke J, Pers TH, Dworzynski P, Keefe K, Niedziela M, Raivio T, Crowley WF Jr, Seminara SB, Quinton R, Hughes VA, Kumanov P, Young J, Yialamas MA, Hall JE, Van Vliet G, Chanoine JP, Rubenstein J, Mohammadi M, Tsai PS, Sidis Y, Lage K, Pitteloud N. Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism. Am J Hum Genet. 2013 May 2;92(5):725-43. doi: 10.1016/j.ajhg.2013.04.008.
- Results publication: PubMed 25394172Villanueva C, Jacobson-Dickman E, Xu C, Manouvrier S, Dwyer AA, Sykiotis GP, Beenken A, Liu Y, Tommiska J, Hu Y, Tiosano D, Gerard M, Leger J, Drouin-Garraud V, Lefebvre H, Polak M, Carel JC, Phan-Hug F, Hauschild M, Plummer L, Rey JP, Raivio T, Bouloux P, Sidis Y, Mohammadi M, de Roux N, Pitteloud N. Congenital hypogonadotropic hypogonadism with split hand/foot malformation: a clinical entity with a high frequency of FGFR1 mutations. Genet Med. 2015 Aug;17(8):651-9. doi: 10.1038/gim.2014.166. Epub 2014 Nov 13.
- Web page for the Principal Investigator Nelly Pitteloud's research groupLink provided by the sponsor.
Related trials for Kallmann Syndrome
RecruitingObservational study
Inherited Reproductive Disorders
Genetic Disorder, Infertility
Active, not recruitingObservational study
Patient and Healthcare Professional Views on Genetic/Genomic Information and Testing
Hypogonadism, Hypogonadotropic, Kallmann Syndrome
RecruitingObservational study
GROWing Up With Rare GENEtic Syndromes
Prader-Willi Syndrome, PWS-like Syndrome
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.
Nelly Pitteloud, M.D. principal investigator
Centre Hositalier Universitaire Vaudois (CHUV)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Kallmann Syndrome and Hypogonadotropic Hypogonadism, run by Centre Hospitalier Universitaire Vaudois at 1 site in Switzerland.
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 9 inclusion and 7 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: looking for participants now, as of the sponsor's last update on 21 Jun 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 Switzerland. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Emmanuelle Paccou (+41 79 556 60 13, emmanuelle.paccou@chuv.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
rare sequence variant(s) in gene(s) (time frame: 1 year (ongoing if no variants are identified)). 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 NCT01601171, which also lists 2 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 21 Jun 2022.