Disorder of Sex Development, 46,XYPhase 3N-of-1 DSDNCT04831099
Testosterone Treatment in a Patient With 17β-hydroxysteroid Dehydrogenase Type 3 Deficiency: an N-of-1 Study
A Phase 3 study testing Testosterone gel in people with Disorder of Sex Development, 46,XY, run by Erasmus Medical Center at 1 site in Netherlands.
Trial summary
A 38-year old women with a 46,XY disorder of sex development (DSD) based on a 17β-hydroxysteroid dehydrogenase type 3 deficiency (17β-HSD3) was seen at the department of Internal Medicine-Endocrinology at the Erasmus MC, Rotterdam, the Netherlands. Read more about this study
- Who is it for?
- Ages 38 years and older, women only
- Conditions the study is for
- Disorder of Sex Development, 46,XY
- What is being tested?
- Testosterone gel
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Jun 2021to 26 Jul 2022
- Phase
- Phase 3
- 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 38 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- N/A
Who cannot join
- N/A
- The study is especially designed for a specific female patient. The patient is 38 years old at the moment. Since the study is especially designed for this patient, there are no formal inclusion and exclusion criteria.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Erasmus MC
Rotterdam, South Holland, 3015GD
Laura de Graaff, MD, PhD, +31618843010, l.degraaff@erasmusmc.nl
Laura de Graaff, MD, PhD
About this study
A 38-year old women with a 46,XY disorder of sex development (DSD) based on a 17β-hydroxysteroid dehydrogenase type 3 deficiency (17β-HSD3) was seen at the department of Internal Medicine-Endocrinology at the Erasmus MC, Rotterdam, the Netherlands.
The patient presented with fatigue, concentration problems and feelings of restlessness. In the past, the patient had undergone a gonadectomy at 9 months of age. In a follow-up visit at the outpatient clinic, the patient mentioned that friends with DSD had successfully been treated with testosterone and the patient requested testosterone treatment for her complaints.
Read more
In the literature, nothing is known about the usefulness of testosterone treatment for women with 17β-HSD3. For other forms of 46,XY DSD like complete androgen insensitivity syndrome (CAIS), limited data are available about testosterone treatment. Two studies have compared the effects of estrogen and testosterone replacement therapy on psychological wellbeing, quality of life (QoL) and sexual function in women with CAIS. The results were not conclusive, as one of them found a positive effect of testosterone replacement therapy on sexual function compared to estrogen, whereas the other study found no differences.
In order to evaluate the effect of testosterone treatment independent of a possible placebo effect, the usefulness of testosterone treatment in this individual patient with 17β-HSD3 will be investigated in an N-of-1 trial in order to improve the clinical care for this patient.
The primary objective is to determine the efficacy of testosterone treatment for fatigue on an individual level in a patient with 17β-HSD3 as assessed with the Checklist Individual Strength (CIS-20).
Read the detailed description
A 38-year old women with a 46,XY disorder of sex development (DSD) based on a 17β-hydroxysteroid dehydrogenase type 3 deficiency (17β-HSD3) was seen at the department of Internal Medicine-Endocrinology at the Erasmus MC, Rotterdam, the Netherlands.
17β-HSD3 is a rare disorder characterized by a (despite the presence of a Y chromosome) female habitus in almost all newborns, with congenital agenesis of the uterus and ovaries. During puberty, patients with 17β-HSD3 often develop secondary male characteristics, such as deepening of the voice, male pattern body hair, and clitoromegaly.
The patient presented with fatigue, concentration problems and feelings of restlessness. In the past, the patient had undergone a gonadectomy at 9 months of age. In a follow-up visit at the outpatient clinic, the patient mentioned that friends with DSD had successfully been treated with testosterone and the patient requested testosterone treatment for her complaints. The patient was aware of the fact that the positive effect noticed by the patients' friends could be (partly) explained by placebo effect.
In the literature, nothing is known about the usefulness of testosterone treatment for women with 17β-HSD3. For other forms of 46,XY DSD like complete androgen insensitivity syndrome (CAIS), limited data are available about testosterone treatment. Two studies have compared the effects of estrogen and testosterone replacement therapy on psychological wellbeing, quality of life (QoL) and sexual function in women with CAIS. The results were not conclusive, as one of them found a positive effect of testosterone replacement therapy on sexual function compared to estrogen, whereas the other study found no differences.
In order to evaluate the effect of testosterone treatment independent of a possible placebo effect, the usefulness of testosterone treatment in this individual patient with 17β-HSD3 will be investigated in an N-of-1 trial in order to improve the clinical care for this patient.
The primary objective is to determine the efficacy of testosterone treatment for fatigue on an individual level in a patient with 17β-HSD3 as assessed with the Checklist Individual Strength (CIS-20).
Secondary objectives are to determine the effect of testosterone treatment on the QoL (5-level EQ-5D), testosterone, dehydroepiandorosterone (DHEA), and estradiol levels, on bone density, and on specific personalized goals that are important to the patient and her environment (Goal Attainment Scaling). To monitor the safety of testosterone treatment, hematocrit levels will be measured and the occurrence of adverse events will be evaluated.
- Conditions
- Disorder of Sex Development, 46,XY
- Being tested
- Testosterone gel, Placebo
- Keywords
- 17-beta-hydroxysteroid dehydrogenase type 3 deficiency
- Medical subject headings
- Disorder of Sex Development, 46,XY
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Testosterone gelDrug
Also called AndroGel
The route of administration is transdermal.
PlaceboDrug
The route of administration is transdermal
| Study group | Role | What they receive |
|---|---|---|
| Testosterone | Experimental | Testosterone gel (20 mg/day) for 8 weeks per period. Receives: Drug: Testosterone gel |
| Placebo | Placebo comparator | Placebo gel (20 mg/day) for 8 weeks per period. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fatigue (Checklist of Individual Strength)
Fatigue is measured with the Checklist of Individual Strength (CIS-20). The CIS-20 consists of 20 questions. The score ranges from 20 - 140. A score of 27-35 means increased fatigue. A score >35 means extreme fatigue.
Measured: Baseline to 420 days
Secondary outcomes (5)
Quality of Life (5-level EQ-5D)
Quality of life is measured with the 5-level EQ-5D (EQ-5D-L5). The range of the EQ-5D-5L is from 0 to 100. A higher score means a better outcome.
Measured: Baseline to 420 days
Laboratory levels
The following laboratory levels will be measured:
- Testosterone (nmol/L)
- Dehydroepiandorosterone (DHEA) (micromol/L)
- Estradiol (pg/mL)
- Hematocrit (%)
Measured: Baseline to 420 days
Bone density
Dual Energy X-ray Absorptiometry scan will be performed to measure bone density.
Measured: Baseline to 420 days
Goal attainment scaling
GAS is an individualized outcome measure in which several personal goals and the corresponding scaling are defined in consultation with the patient. The scaling is standardized, which makes it possible to reliably measure the change in the situation of the patient. The levels range from -3 to +2. A higher level means a better outcome. The predefined personal goals are a measure of the effectivity of the treatment. If possible, three goals will be set.
Measured: Baseline to 420 days
Number of adverse events
All adverse events that occur from start of treatment until 30 days after last administration will be described to assess the safety of testosterone treatment. Adverse events are defined as any undesirable experience occurring during the study, whether or not considered related to testosterone treatment
Measured: Baseline to 450 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2021
- Study start1 Jun 2021 (estimated)
- Primary completion26 Jul 2022 (estimated)
- Study completion26 Jul 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Disorder of Sex Development, 46,XYStudies of the same condition, open and under way.
- More trials run by Erasmus Medical CenterThe 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
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- N-of-1 study: cross-over study in 1 patient with 2 cycles that each consists of 2 periods (one period of placebo and one period of active treatment).
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, dr. Laura C. G. de Graaff-Herder, Erasmus Medical Center
- Investigators
- Laura de Graaff, MD, PhD, Principal investigator, Department of Internal Medicine - Endocrinology, Erasmus MC, Rotterdam, the Netherlands
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04831099
- Sponsor's protocol ID
- N-of-1 DSD
- Acronym
- N-of-1 DSD
- Status last verified
- Apr 2021
- First submitted
- 26 Mar 2021
- Last updated
- 5 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data is available upon reasonable request.
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Testosterone Treatment in a Patient With 17β-hydroxysteroid Dehydrogenase Type 3 Deficiency: an N-of-1 Study
- ClinicalTrials.gov ID
- NCT04831099
- Acronym / sponsor ID
- N-of-1 DSD / N-of-1 DSD
- Conditions
- Disorder of Sex Development, 46,XY
- Keywords
- 17-beta-hydroxysteroid dehydrogenase type 3 deficiency
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 1 participants (estimated)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Study start
- 1 Jun 2021 (estimated)
- Primary completion
- 26 Jul 2022 (estimated)
- Study completion
- 26 Jul 2022 (estimated)
- First posted
- 5 Apr 2021 (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.
A 38-year old women with a 46,XY disorder of sex development (DSD) based on a 17β-hydroxysteroid dehydrogenase type 3 deficiency (17β-HSD3) was seen at the department of Internal Medicine-Endocrinology at the Erasmus MC, Rotterdam, the Netherlands.
The patient presented with fatigue, concentration problems and feelings of restlessness. In the past, the patient had undergone a gonadectomy at 9 months of age. In a follow-up visit at the outpatient clinic, the patient mentioned that friends with DSD had successfully been treated with testosterone and the patient requested testosterone treatment for her complaints.
In the literature, nothing is known about the usefulness of testosterone treatment for women with 17β-HSD3. For other forms of 46,XY DSD like complete androgen insensitivity syndrome (CAIS), limited data are available about testosterone treatment. Two studies have compared the effects of estrogen and testosterone replacement therapy on psychological wellbeing, quality of life (QoL) and sexual function in women with CAIS. The results were not conclusive, as one of them found a positive effect of testosterone replacement therapy on sexual function compared to estrogen, whereas the other study found no differences.
In order to evaluate the effect of testosterone treatment independent of a possible placebo effect, the usefulness of testosterone treatment in this individual patient with 17β-HSD3 will be investigated in an N-of-1 trial in order to improve the clinical care for this patient.
The primary objective is to determine the efficacy of testosterone treatment for fatigue on an individual level in a patient with 17β-HSD3 as assessed with the Checklist Individual Strength (CIS-20).
Detailed description
A 38-year old women with a 46,XY disorder of sex development (DSD) based on a 17β-hydroxysteroid dehydrogenase type 3 deficiency (17β-HSD3) was seen at the department of Internal Medicine-Endocrinology at the Erasmus MC, Rotterdam, the Netherlands.
17β-HSD3 is a rare disorder characterized by a (despite the presence of a Y chromosome) female habitus in almost all newborns, with congenital agenesis of the uterus and ovaries. During puberty, patients with 17β-HSD3 often develop secondary male characteristics, such as deepening of the voice, male pattern body hair, and clitoromegaly.
The patient presented with fatigue, concentration problems and feelings of restlessness. In the past, the patient had undergone a gonadectomy at 9 months of age. In a follow-up visit at the outpatient clinic, the patient mentioned that friends with DSD had successfully been treated with testosterone and the patient requested testosterone treatment for her complaints. The patient was aware of the fact that the positive effect noticed by the patients' friends could be (partly) explained by placebo effect.
In the literature, nothing is known about the usefulness of testosterone treatment for women with 17β-HSD3. For other forms of 46,XY DSD like complete androgen insensitivity syndrome (CAIS), limited data are available about testosterone treatment. Two studies have compared the effects of estrogen and testosterone replacement therapy on psychological wellbeing, quality of life (QoL) and sexual function in women with CAIS. The results were not conclusive, as one of them found a positive effect of testosterone replacement therapy on sexual function compared to estrogen, whereas the other study found no differences.
In order to evaluate the effect of testosterone treatment independent of a possible placebo effect, the usefulness of testosterone treatment in this individual patient with 17β-HSD3 will be investigated in an N-of-1 trial in order to improve the clinical care for this patient.
The primary objective is to determine the efficacy of testosterone treatment for fatigue on an individual level in a patient with 17β-HSD3 as assessed with the Checklist Individual Strength (CIS-20).
Secondary objectives are to determine the effect of testosterone treatment on the QoL (5-level EQ-5D), testosterone, dehydroepiandorosterone (DHEA), and estradiol levels, on bone density, and on specific personalized goals that are important to the patient and her environment (Goal Attainment Scaling). To monitor the safety of testosterone treatment, hematocrit levels will be measured and the occurrence of adverse events will be evaluated.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- N-of-1 study: cross-over study in 1 patient with 2 cycles that each consists of 2 periods (one period of placebo and one period of active treatment).
| Arm | Type | Receives |
|---|---|---|
| Testosterone | Experimental | Drug: Testosterone gelTestosterone gel (20 mg/day) for 8 weeks per period. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo gel (20 mg/day) for 8 weeks per period. |
Who may qualify
- Ages
- 38 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- N/A
Key exclusion criteria (2 listed)
- N/A
- The study is especially designed for a specific female patient. The patient is 38 years old at the moment. Since the study is especially designed for this patient, there are no formal inclusion and exclusion criteria.
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 |
|---|---|---|
| Testosterone gelAlso: AndroGelThe route of administration is transdermal. | Drug | Testosterone |
| PlaceboThe route of administration is transdermal | Drug | Placebo |
Primary outcome
Fatigue (Checklist of Individual Strength)
Time frame: Baseline to 420 days
Fatigue is measured with the Checklist of Individual Strength (CIS-20). The CIS-20 consists of 20 questions. The score ranges from 20 - 140. A score of 27-35 means increased fatigue. A score >35 means extreme fatigue.
5 secondary outcomes
Quality of Life (5-level EQ-5D)
Time frame: Baseline to 420 days
Laboratory levels
Time frame: Baseline to 420 days
Bone density
Time frame: Baseline to 420 days
Goal attainment scaling
Time frame: Baseline to 420 days
Number of adverse events
Time frame: Baseline to 450 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2021.
- Individual participant dataSharing planned: Yes. Individual participant data is available upon reasonable request.
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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.
Laura de Graaff, MD, PhD principal investigator
Department of Internal Medicine - Endocrinology, Erasmus MC, Rotterdam, the Netherlands
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Testosterone gel in people with Disorder of Sex Development, 46,XY, run by Erasmus Medical Center at 1 site in Netherlands.
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 1 inclusion and 2 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: status not confirmed, as of the sponsor's last update on 5 Apr 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 Netherlands. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Laura de Graaff, MD, PhD (+31618843010, l.degraaff@erasmusmc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fatigue (Checklist of Individual Strength) (time frame: Baseline to 420 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Apr 2021.