Hypogonadism, MaleEarly Phase 1NCT04717362
The Effects of Natesto For Treatment Of Hypogonadism
A Early Phase 1 study testing Natesto Nasal Product in people with Hypogonadism, Male and Infertility, Male, run by Baylor College of Medicine.
Trial summary
In this prospective study, the investigators plan is to confirm the role of Natesto (intranasal testosterone) to combat hypogonadal symptoms in men trying to recover spermatogenesis following the withdrawal of conventional Testosterone replacement therapy. Read more about this study
- Who is it for?
- Ages 18 to 40 years, men only
- Conditions the study is for
- Hypogonadism, Male, Infertility, Male, Testosterone Deficiency
- What is being tested?
- Natesto Nasal Product
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Mar 2024to 31 Dec 2024
- Phase
- Early Phase 1
- 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 18 to 40 years
- Men only
- No healthy volunteers
- Adult
Who may be able to join
- 1. Voluntarily sign and date the study consent form(s) which have been approved by an Institutional Review Board (IRB). Written consent must be obtained prior to the initiation of any study procedures.
- 2. Male between 18 and 64 years of age, inclusive, with documented onset of testosterone induced hypogonadism with impaired semen parameters who are attempting to achieve a successful pregnancy.
- 3. Documented diagnosis of primary hypogonadism (congenital or acquired) or hypogonadotropic hypogonadism (congenital or acquired).
- 4. Serum total testosterone < 350 ng/dL based on 2 consecutive blood samples obtained 1-4 weeks apart between 6 and 10 AM following an appropriate washout of current androgen replacement therapy; with clinical symptoms of hypogonadism such as diminished energy and sexual function; and/or a decreased sperm count (<20 million sperm/mL semen).
- 5. Discontinued current testosterone replacement treatment and completed a washout of 4 weeks following androgen treatment (excluding Testopel TM). Washout must be completed prior to collection of baseline serum testosterone samples to determine study eligibility.
- 6. Judged to be in good general health as determined by the principal investigator based upon the results of a medical history, physical examination, vital signs, and laboratory profile.
Who cannot join
- 1. History of significant sensitivity or allergy to androgens, castor oil or product excipients.
- 2. Clinically significant findings in the pre-study examinations including abnormal breast examination requiring follow-up.
- 3. Abnormal prostate digital rectal examination (DRE) with palpable nodule(s) or I-PSS score > 19 points.
- 4. Body mass index (BMI) ≥ 35 kg/m2.
- 5. History of vasectomy.
- 6. Clinically significant abnormal laboratory value, in the opinion of the investigator, in serum chemistry, hematology, or urinalysis including but not limited to:
Show all 21Show fewer
- Baseline hemoglobin > 16 g/dL
- Hematocrit < 35% or > 50%
- PSA > 4 ng/mL and age >40
- 7. History of seizures or convulsions, including febrile, alcohol or drug withdrawal seizures.
- 8. History of any clinically significant illness, infection, or surgical procedure within 4 weeks prior to study drug administration.
- 9. History of stroke or myocardial infarction within the past 5 years.
- 10. History of, or current or suspected, prostate or breast cancer.
- 11. History of diagnosed, severe, untreated, obstructive sleep apnea.
- 12. History of abuse of alcohol or any drug substance in the opinion of the investigator within the previous 2 years.
- 13. History of nasal disorders such as nasal polyps; nasal septal perforation; nasal surgery; nasal trauma resulting in nasal fracture within the previous 6 months or nasal fracture that caused a deviated anterior nasal septum; sinus surgery or sinus disease
- 14. Donation or loss of 550 mL or more blood volume (including plasmapheresis) or receipt of a transfusion of any blood product within 12 weeks prior to the start of treatment.
- 15. Inadequate venous access for collection of serial blood samples required for pharmacokinetic profiles.
- 16. Receipt of any investigational product within 4 weeks or within 5 half-lives prior to the start of treatment.
- 17. Inability to understand and provide written informed consent for the study.
- 18. Considered by the investigator or the sponsor-designated physician, for any reason, that the subject is an unsuitable candidate to receive Natesto.
About this study
Official title: The Effects of Natesto For Treatment Of Hypogonadism On Maintenance Of Spermatogensis.
In this prospective study, the investigators plan is to confirm the role of Natesto (intranasal testosterone) to combat hypogonadal symptoms in men trying to recover spermatogenesis following the withdrawal of conventional Testosterone replacement therapy.
Read the detailed description
Testosterone replacement therapy (TTh) is becoming increasingly common among men of reproductive age in the United States. An estimated 3 million men are on TTh; however exogenous testosterone use can disrupt the hypothalamus-pituitary-gonadal (HPG) axis, leading to reduced spermatogenesis and possible infertility. In normal physiology, the hypothalamus releases Gonadotropin-releasing hormone (GnRH), which stimulates the anterior pituitary to release Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH). FSH then stimulates the Sertoli cells in the testis to support spermatogonial differentiation and maturation. LH stimulates the Leydig cells in the testes to produce endogenous testosterone. Regulation of this HPG axis occurs via negative feedback where testosterone directly inhibits the release of GnRH and LH from the hypothalamus and pituitary, respectively. The use of exogenous testosterone thus leads to reduced Sertoli function causing diminished spermatogenesis.
The spontaneous recovery of spermatogenesis after cessation of TTh is possible but may take months to years and cause the patient to experience new onset of severe hypothalamic hypogonadal symptoms. Human chorionic gonadotropin (HCG) is a naturally occurring protein that mimics LH and may be used as a therapy to support the return of spermatogenesis quickly with minimal side effects and resolve hypogonadal symptoms. Studies have shown that testosterone-induced infertile patients can recover sperm in the ejaculate in 4.6 months when treated with HCG supplemented with clomiphene citrate, tamoxifen, anastrozole, or recombinant FSH. With the cessation of TTh, despite the use of LH stimulatory protocols, these patients still experience hypogonadal symptoms. Recent preliminary results show the potential to offset hypogonadism symptoms that accompany exogenous testosterone cessation through administration of 4.5% intranasal testosterone gel. Natesto is a nasally administered exogenous 4.5% testosterone gel, administered from a non-pressurized, manual pump dispenser equipped with a specialized nasal applicator which administers 125uL (5.5mg of testosterone). Previous studies have shown that a single nasal dose has a rapid absorption with a Tmax at 60 mins and a half-life that ranged between 10-100 minutes. Three to four daily doses achieve eugonadal levels of circulating testosterone comparable to normal pulsatile-regulated release of testosterone. It has also been shown that men on Natesto maintain FSH and LH levels as well as total motile sperm count within the normal range. In this prospective study, the investigators seek to confirm the role of Natesto to combat hypogonadal symptoms in men trying to recover spermatogenesis following the withdrawal of conventional TTh.
- Being tested
- Natesto Nasal Product
- Keywords
- Natesto, Male, Hypogonadism, Sexual Medicine
- Medical subject headings
- Eunuchism, Infertility, Male, Hypogonadism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Natesto Nasal ProductDrug
Nasally administered exogenous 4.5% testosterone gel, administered from a non-pressurized, manual pump dispenser equipped with a specialized nasal applicator which administers 125uL (5.5mg of testosterone).
| Study group | Role | What they receive |
|---|---|---|
| Standard Reboot with Natesto | Experimental | Standard Reboot Protocol + Natesto Receives: Drug: Natesto Nasal Product |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Semen Analysis
Change in Total Motile Sperm
Measured: Baseline, 14 weeks, 26 weeks.
Secondary outcomes (7)
Change in Hypogonadal Panel
change in blood LH levels
Measured: Baseline, 14 weeks, 26 weeks.
Change in Hypogonadal Panel
change in blood FSH levels
Measured: Baseline, 14 weeks, 26 weeks.
Change Hypogonadal Panel
change in blood Testosterone levels
Measured: Baseline, 14 weeks, 26 weeks.
Change in Hypogonadal Panel
change in blood E2 levels
Measured: Baseline, 14 weeks, 26 weeks.
Change in Quality of Life Questionnaire
Change in SF36 score
Measured: Baseline, 14 weeks, 26 weeks.
Change in Quality of Life Questionnaire
Change in IPSS score
Measured: Baseline, 14 weeks, 26 weeks.
Change in Quality of Life Questionnaire
Change in IIEF score
Measured: Baseline, 14 weeks, 26 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2021
- Study start1 Mar 2024 (estimated)
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2024 (estimated)
Why it stopped: No longer wanting to enroll or start study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hypogonadism, MaleStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Prospective non-blinded study
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Larry I. Lipshultz, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04717362
- Sponsor's protocol ID
- 48763
- Status last verified
- Apr 2024
- First submitted
- 7 Dec 2020
- Last updated
- 24 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Natesto For Treatment Of Hypogonadism On Maintenance Of Spermatogensis.
- ClinicalTrials.gov ID
- NCT04717362
- Acronym / sponsor ID
- 48763
- Keywords
- Natesto, Male, Hypogonadism, Sexual Medicine
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No longer wanting to enroll or start study.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Study start
- 1 Mar 2024 (estimated)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 22 Jan 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.
In this prospective study, the investigators plan is to confirm the role of Natesto (intranasal testosterone) to combat hypogonadal symptoms in men trying to recover spermatogenesis following the withdrawal of conventional Testosterone replacement therapy.
Detailed description
Testosterone replacement therapy (TTh) is becoming increasingly common among men of reproductive age in the United States. An estimated 3 million men are on TTh; however exogenous testosterone use can disrupt the hypothalamus-pituitary-gonadal (HPG) axis, leading to reduced spermatogenesis and possible infertility. In normal physiology, the hypothalamus releases Gonadotropin-releasing hormone (GnRH), which stimulates the anterior pituitary to release Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH). FSH then stimulates the Sertoli cells in the testis to support spermatogonial differentiation and maturation. LH stimulates the Leydig cells in the testes to produce endogenous testosterone. Regulation of this HPG axis occurs via negative feedback where testosterone directly inhibits the release of GnRH and LH from the hypothalamus and pituitary, respectively. The use of exogenous testosterone thus leads to reduced Sertoli function causing diminished spermatogenesis.
The spontaneous recovery of spermatogenesis after cessation of TTh is possible but may take months to years and cause the patient to experience new onset of severe hypothalamic hypogonadal symptoms. Human chorionic gonadotropin (HCG) is a naturally occurring protein that mimics LH and may be used as a therapy to support the return of spermatogenesis quickly with minimal side effects and resolve hypogonadal symptoms. Studies have shown that testosterone-induced infertile patients can recover sperm in the ejaculate in 4.6 months when treated with HCG supplemented with clomiphene citrate, tamoxifen, anastrozole, or recombinant FSH. With the cessation of TTh, despite the use of LH stimulatory protocols, these patients still experience hypogonadal symptoms. Recent preliminary results show the potential to offset hypogonadism symptoms that accompany exogenous testosterone cessation through administration of 4.5% intranasal testosterone gel. Natesto is a nasally administered exogenous 4.5% testosterone gel, administered from a non-pressurized, manual pump dispenser equipped with a specialized nasal applicator which administers 125uL (5.5mg of testosterone). Previous studies have shown that a single nasal dose has a rapid absorption with a Tmax at 60 mins and a half-life that ranged between 10-100 minutes. Three to four daily doses achieve eugonadal levels of circulating testosterone comparable to normal pulsatile-regulated release of testosterone. It has also been shown that men on Natesto maintain FSH and LH levels as well as total motile sperm count within the normal range. In this prospective study, the investigators seek to confirm the role of Natesto to combat hypogonadal symptoms in men trying to recover spermatogenesis following the withdrawal of conventional TTh.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Prospective non-blinded study
| Arm | Type | Receives |
|---|---|---|
| Standard Reboot with Natesto | Experimental | Drug: Natesto Nasal ProductStandard Reboot Protocol + Natesto |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 1. Voluntarily sign and date the study consent form(s) which have been approved by an Institutional Review Board (IRB). Written consent must be obtained prior to the initiation of any study procedures.
- 2. Male between 18 and 64 years of age, inclusive, with documented onset of testosterone induced hypogonadism with impaired semen parameters who are attempting to achieve a successful pregnancy.
- 3. Documented diagnosis of primary hypogonadism (congenital or acquired) or hypogonadotropic hypogonadism (congenital or acquired).
- 4. Serum total testosterone < 350 ng/dL based on 2 consecutive blood samples obtained 1-4 weeks apart between 6 and 10 AM following an appropriate washout of current androgen replacement therapy; with clinical symptoms of hypogonadism such as diminished energy and sexual function; and/or a decreased sperm count (<20 million sperm/mL semen).
- 5. Discontinued current testosterone replacement treatment and completed a washout of 4 weeks following androgen treatment (excluding Testopel TM). Washout must be completed prior to collection of baseline serum testosterone samples to determine study eligibility.
Key exclusion criteria (21 listed)
- 1. History of significant sensitivity or allergy to androgens, castor oil or product excipients.
- 2. Clinically significant findings in the pre-study examinations including abnormal breast examination requiring follow-up.
- 3. Abnormal prostate digital rectal examination (DRE) with palpable nodule(s) or I-PSS score > 19 points.
- 4. Body mass index (BMI) ≥ 35 kg/m2.
- 5. History of vasectomy.
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 |
|---|---|---|
| Natesto Nasal ProductNasally administered exogenous 4.5% testosterone gel, administered from a non-pressurized, manual pump dispenser equipped with a specialized nasal applicator which administers 125uL (5.5mg of testosterone). | Drug | Standard Reboot with Natesto |
Primary outcome
Change in Semen Analysis
Time frame: Baseline, 14 weeks, 26 weeks.
Change in Total Motile Sperm
7 secondary outcomes
Change in Hypogonadal Panel
Time frame: Baseline, 14 weeks, 26 weeks.
Change in Hypogonadal Panel
Time frame: Baseline, 14 weeks, 26 weeks.
Change Hypogonadal Panel
Time frame: Baseline, 14 weeks, 26 weeks.
Change in Hypogonadal Panel
Time frame: Baseline, 14 weeks, 26 weeks.
Change in Quality of Life Questionnaire
Time frame: Baseline, 14 weeks, 26 weeks.
Change in Quality of Life Questionnaire
Time frame: Baseline, 14 weeks, 26 weeks.
Change in Quality of Life Questionnaire
Time frame: Baseline, 14 weeks, 26 weeks.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2024.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Natesto Nasal Product in people with Hypogonadism, Male and Infertility, Male, run by Baylor College of Medicine.
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 6 inclusion and 21 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: withdrawn, as of the sponsor's last update on 24 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Change in Semen Analysis (time frame: Baseline, 14 weeks, 26 weeks.). 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 24 Apr 2024.