Hypogonadotropic Hypogonadism
Conditions
Keywords
hypogonadotropic hypogonadism
Brief summary
Over the last few years, studies have shown that men with type 2 diabetes sometimes develop a condition called hypogonadotrophic hypogonadism (HH). People with this condition produce little or no sex hormones. Obesity and metabolic syndrome are also associated with HH. Research suggests that insulin in the brain may benefit the glands that release these hormones. During this study, subjects will spray a small amount of insulin into their nose.This will increase insulin concentrations in the brain. The purpose of this study is to find out the effect of one dose of intranasal insulin on release of LH (a sex hormone) in obese diabetic men with HH.
Detailed description
Studies over the last few years have clearly established that at least 25% of men with type 2 diabetes have subnormal free testosterone (T) concentrations in association with inappropriately low leutinizing hormone (LH) and FSH (follicle stimulating hormone) concentrations. These patients thus suffer from hypogonadotrophic hypogonadism (HH). Obesity and metabolic syndrome are also associated with HH. Animal studies and in vitro data have shown that insulin action and insulin responsiveness in the brain are necessary for the maintenance of the functional integrity of the hypothalamo-hypophyseal-gonadal axis. Insulin concentrations can be increased in the brain by delivering insulin intranasally with vianase device. The aim of this project is to study the effect of one dose of intranasal insulin on release of LH in obese diabetic men with HH. 15 obese men with type 2 diabetes and low free T along with normal LH concentrations will be recruited for the study. The study will be carried out at the clinical center of Texas Tech (Odessa campus). There will be two study visits, each comprising of blood tests every 15 minutes over 6 hours. 40 IU of intranasal insulin or saline will be given after a baseline period of blood sampling of 2 hours. Student's t-test will be used to compare the change in LH concentrations after intranasal saline or insulin.
Interventions
DRUGintranasal insulin
insulin
DRUGplacebo (intranasal saline)
saline
Sponsors
Texas Tech University Health Sciences Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Males age 18 to 75 years * Obesity (BMI ≥30 kg/m2) * Type 2 diabetes * Hypogonadotropic hypogonadism defined as calculated free testosterone concentrations below 7 ng/dl along with normal or low LH concentrations
Exclusion criteria
* HbA1c\>8.5% * Use of preprandial insulin therapy * Use of testosterone currently or in the past 4 months * Use of over the counter health supplements which contain androgens * Use of corticosteroids or narcotics in the past 3 months * Coronary event or procedure(myocardial infarction, unstable angina, coronary artery bypass, surgery or coronary angioplasty) in the previous twelve weeks * Type I Diabetes * Currently suffering from foot ulcer, significant periodontal disease or any other chronic infectious or inflammatory condition * Hepatic disease (transaminase \> 3 times normal) or cirrhosis * Renal impairment (defined as glomerular filtration rate\<30) * HIV or Hepatitis C positive status * Any other life-threatening, non-cardiac disease * History of untreated severe obstructive sleep apnea(defined as apnea-hypopnea index ≥30) * currently suffering from symptomatic depression, with or without treatment * Use of an investigational agent or therapeutic regimen within 30 days of study * Participation in any other concurrent clinical trial * Pituitary tumor/damage/ other trophic hormone deficiency
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| LH | 4 hours | Luteinizing hormone (LH) concentrations after intranasal insulin as compared to placebo (intranasal saline). This endpoint was measured in both arms |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Diabetes All patients will be randomized to receive either insulin or saline at first visit and alternate treatment at the second visit
intranasal insulin
placebo (intranasal saline) | 8 |
| Control All control subjects will be randomized to receive either insulin or saline at first visit and alternate treatment at the second visit
intranasal insulin
placebo (intranasal saline) | 6 |
| Total | 14 |
Baseline characteristics
| Characteristic | Diabetes | Control | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 6 Participants | 13 Participants |
| Age, Continuous | 63 years STANDARD_DEVIATION 7 | 30 years STANDARD_DEVIATION 9 | 48 years STANDARD_DEVIATION 18 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 2 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 4 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 8 participants | 6 participants | 14 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 6 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 6 |
| other Total, other adverse events | 0 / 8 | 0 / 6 |
| serious Total, serious adverse events | 0 / 8 | 0 / 6 |
Outcome results
Primary
LH
Luteinizing hormone (LH) concentrations after intranasal insulin as compared to placebo (intranasal saline). This endpoint was measured in both arms
Time frame: 4 hours
Population: diabetes
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Diabetes | LH | baseline | 7.7 IU/L | Standard Deviation 3 |
| Diabetes | LH | post-intervention saline | 7.9 IU/L | Standard Deviation 4.3 |
| Diabetes | LH | post-intervention insulin | 8 IU/L | Standard Deviation 3.4 |
| Control | LH | baseline | 3.3 IU/L | Standard Deviation 1.4 |
| Control | LH | post-intervention saline | 3.8 IU/L | Standard Deviation 1.4 |
| Control | LH | post-intervention insulin | 3.4 IU/L | Standard Deviation 1.2 |