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The Effects of Natesto For Treatment Of Hypogonadism

Studies

Study First Submitted Date 2020-12-07
Study First Posted Date 2021-01-22
Last Update Posted Date 2023-05-11
Start Month Year March 1, 2024
Primary Completion Month Year December 31, 2024
Verification Month Year May 2023
Verification Date 2023-05-31
Last Update Posted Date 2023-05-11

Detailed Descriptions

Sequence: 20594218
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.

Browse Interventions

Sequence: 95402474 Sequence: 95402467 Sequence: 95402468 Sequence: 95402469 Sequence: 95402470 Sequence: 95402471 Sequence: 95402472 Sequence: 95402473 Sequence: 95402475 Sequence: 95402476 Sequence: 95402477 Sequence: 95402478
Mesh Term Anabolic Agents Mesh Term Methyltestosterone Mesh Term Testosterone 17 beta-cypionate Mesh Term Testosterone Mesh Term Testosterone undecanoate Mesh Term Testosterone enanthate Mesh Term Antineoplastic Agents, Hormonal Mesh Term Antineoplastic Agents Mesh Term Hormones Mesh Term Hormones, Hormone Substitutes, and Hormone Antagonists Mesh Term Physiological Effects of Drugs Mesh Term Androgens
Downcase Mesh Term anabolic agents Downcase Mesh Term methyltestosterone Downcase Mesh Term testosterone 17 beta-cypionate Downcase Mesh Term testosterone Downcase Mesh Term testosterone undecanoate Downcase Mesh Term testosterone enanthate Downcase Mesh Term antineoplastic agents, hormonal Downcase Mesh Term antineoplastic agents Downcase Mesh Term hormones Downcase Mesh Term hormones, hormone substitutes, and hormone antagonists Downcase Mesh Term physiological effects of drugs Downcase Mesh Term androgens
Mesh Type mesh-ancestor Mesh Type mesh-list Mesh Type mesh-list Mesh Type mesh-list Mesh Type mesh-list Mesh Type mesh-list Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor

Conditions

Sequence: 51843756 Sequence: 51843757 Sequence: 51843758
Name Hypogonadism, Male Name Infertility, Male Name Testosterone Deficiency
Downcase Name hypogonadism, male Downcase Name infertility, male Downcase Name testosterone deficiency

Id Information

Sequence: 39896937
Id Source org_study_id
Id Value 48763

Design Groups

Sequence: 55269459
Group Type Experimental
Title Standard Reboot with Natesto
Description Standard Reboot Protocol + Natesto

Interventions

Sequence: 52164447
Intervention Type Drug
Name Natesto Nasal Product
Description 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).

Keywords

Sequence: 79335602 Sequence: 79335603 Sequence: 79335604 Sequence: 79335605
Name Natesto Name Male Name Hypogonadism Name Sexual Medicine
Downcase Name natesto Downcase Name male Downcase Name hypogonadism Downcase Name sexual medicine

Design Outcomes

Sequence: 176317879 Sequence: 176317880 Sequence: 176317881 Sequence: 176317882 Sequence: 176317883 Sequence: 176317884 Sequence: 176317885 Sequence: 176317886
Outcome Type primary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary
Measure Change in Semen Analysis Measure Change in Hypogonadal Panel Measure Change in Hypogonadal Panel Measure Change Hypogonadal Panel Measure Change in Hypogonadal Panel Measure Change in Quality of Life Questionnaire Measure Change in Quality of Life Questionnaire Measure Change in Quality of Life Questionnaire
Time Frame Baseline, 14 weeks, 26 weeks. Time Frame Baseline, 14 weeks, 26 weeks. Time Frame Baseline, 14 weeks, 26 weeks. Time Frame Baseline, 14 weeks, 26 weeks. Time Frame Baseline, 14 weeks, 26 weeks. Time Frame Baseline, 14 weeks, 26 weeks. Time Frame Baseline, 14 weeks, 26 weeks. Time Frame Baseline, 14 weeks, 26 weeks.
Description Change in Total Motile Sperm Description change in blood LH levels Description change in blood FSH levels Description change in blood Testosterone levels Description change in blood E2 levels Description Change in SF36 score Description Change in IPSS score Description Change in IIEF score

Browse Conditions

Sequence: 192166004 Sequence: 192166001 Sequence: 192166002 Sequence: 192166003 Sequence: 192166005 Sequence: 192166006 Sequence: 192166007 Sequence: 192166008 Sequence: 192166009 Sequence: 192166010
Mesh Term Eunuchism Mesh Term Infertility Mesh Term Infertility, Male Mesh Term Hypogonadism Mesh Term Genital Diseases Mesh Term Urogenital Diseases Mesh Term Gonadal Disorders Mesh Term Endocrine System Diseases Mesh Term Genital Diseases, Male Mesh Term Male Urogenital Diseases
Downcase Mesh Term eunuchism Downcase Mesh Term infertility Downcase Mesh Term infertility, male Downcase Mesh Term hypogonadism Downcase Mesh Term genital diseases Downcase Mesh Term urogenital diseases Downcase Mesh Term gonadal disorders Downcase Mesh Term endocrine system diseases Downcase Mesh Term genital diseases, male Downcase Mesh Term male urogenital diseases
Mesh Type mesh-list Mesh Type mesh-list Mesh Type mesh-list Mesh Type mesh-list Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor

Sponsors

Sequence: 48016117
Agency Class OTHER
Lead Or Collaborator lead
Name Baylor College of Medicine

Central Contacts

Sequence: 11941693
Contact Type primary
Name Larry Lipshultz, MD
Phone 713-798-6270
Email Larryl@bcm.edu
Role Contact

Design Group Interventions

Sequence: 67755139
Design Group Id 55269459
Intervention Id 52164447

Eligibilities

Sequence: 30573804
Gender Male
Minimum Age 18 Years
Maximum Age 40 Years
Healthy Volunteers No
Criteria Inclusion Criteria: 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. Exclusion Criteria: 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: 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.
Adult True
Child False
Older Adult False

Calculated Values

Sequence: 254293253
Registered In Calendar Year 2020
Were Results Reported False
Has Single Facility False
Minimum Age Num 18
Maximum Age Num 40
Minimum Age Unit Years
Maximum Age Unit Years
Number Of Primary Outcomes To Measure 1
Number Of Secondary Outcomes To Measure 7

Designs

Sequence: 30322015
Allocation N/A
Intervention Model Single Group Assignment
Observational Model
Primary Purpose Treatment
Time Perspective
Masking None (Open Label)
Intervention Model Description Prospective non-blinded study

Responsible Parties

Sequence: 28700734
Responsible Party Type Principal Investigator
Name Larry I. Lipshultz
Title rofessor of Urology and Chief of the Scott Department of Urology's Division of Male Reproductive Medicine and Surgery
Affiliation Baylor College of Medicine