Effect of Intranasal Insulin on LH Concentrations in Man

• Sponsor: Texas Tech University Health Sciences Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02154477
• Collaborator: (none)
• Enrollment: 14
• Location: 1
• Arms: 2
• Actual Duration (Months): 36
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hypogonadotropic Hypogonadism	Drug: intranasal insulin; Drug: placebo (intranasal saline)	Phase 1/Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Effect of Intranasal Insulin on LH Concentrations in Man
• Actual Study Start Date: Dec 1, 2014
• Actual Primary Completion Date: Dec 1, 2017
• Actual Study Completion Date: Dec 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: diabetes All patient will receive insulin at one visit and saline at another visit	Drug: intranasal insulin; insulin; Drug: placebo (intranasal saline); saline
Active Comparator: control All patient will receive insulin at one visit and saline at another visit	Drug: intranasal insulin; insulin; Drug: placebo (intranasal saline); saline

Outcome Measures

Primary Outcome Measures

1. LH [4 hours]

   Luteinizing hormone (LH) concentrations after intranasal insulin as compared to placebo (intranasal saline). This endpoint was measured in both arms

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: Male
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	TTTUHSC-Permian Basin	Odessa	Texas	United States	79763

Sponsors and Collaborators

• Texas Tech University Health Sciences Center

Investigators

• Principal Investigator: Sandeep Dhindsa, MD, TTUHSC

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 29, 2015

More Information

Publications

None provided.

• Responsible Party: Texas Tech University Health Sciences Center
• ClinicalTrials.gov Identifier: NCT02154477
• Other Study ID Numbers: L14-075
• First Posted: Jun 3, 2014
• Last Update Posted: Aug 13, 2019
• Last Verified: Jul 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Texas Tech University Health Sciences Center: hypogonadotropic hypogonadism
• Additional relevant MeSH terms: Hypogonadism; Insulin

Study Results

Participant Flow

Arm/Group Title	Control	Diabetes
Arm/Group Description	lean healthy men, randomized to receive saline or insulin at first visit and the alternate treatment at second visit	men with diabetes, randomized to receive saline or insulin at first visit and the alternate treatment at second visit
Period Title: Overall Study
STARTED	6	8
COMPLETED	6	8
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Diabetes	Control	Total
Arm/Group Description	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)	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)	Total of all reporting groups
Overall Participants	8	6	14
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	7 87.5%	6 100%	13 92.9%
>=65 years	1 12.5%	0 0%	1 7.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63 (7)	30 (9)	48 (18)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	8 100%	6 100%	14 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 50%	2 33.3%	6 42.9%
Not Hispanic or Latino	4 50%	4 66.7%	8 57.1%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	8 100%	6 100%	14 100%

Outcome Measures

1. Primary Outcome

Title	LH
Description	Luteinizing hormone (LH) concentrations after intranasal insulin as compared to placebo (intranasal saline). This endpoint was measured in both arms
Time Frame	4 hours

Outcome Measure Data

Analysis Population Description

diabetes

Arm/Group Title	Diabetes	Control
Arm/Group Description	All patient will receive insulin at one visit and saline at another visit intranasal insulin placebo (intranasal saline)	lean healthy men. All men will receive insulin at one visit and saline at the other.
Measure Participants	8	6
baseline	7.7 (3)	3.3 (1.4)
post-intervention saline	7.9 (4.3)	3.8 (1.4)
post-intervention insulin	8 (3.4)	3.4 (1.2)

Adverse Events

Time Frame	4 hours
Adverse Event Reporting Description	hypoglycemia
Arm/Group Title	Diabetes		Control
Arm/Group Description	All diabetes patients were randomized to receive either insulin or saline at one visit and the alternate treatment at the second visit. intranasal insulin placebo (intranasal saline)		All control subjects were randomized to receive either insulin or saline at one visit and the alternate treatment at the second visit. intranasal insulin placebo (intranasal saline)
All Cause Mortality
	Diabetes		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/6 (0%)
Serious Adverse Events
	Diabetes		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Diabetes		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/6 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.