Effect of Intranasal Insulin on LH Concentrations in Man

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.

Study Overview

• Status: Completed
• Conditions: Hypogonadotropic Hypogonadism
• Intervention / Treatment: Drug: intranasal insulin; Drug: placebo (intranasal saline)

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 Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Odessa, Texas, United States, 79763
      • TTTUHSC-Permian Basin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Texas Tech University Health Sciences Center
• Investigators: Principal Investigator: Sandeep Dhindsa, MD, TTUHSC

Publications and helpful links

General Publications

• Dhindsa S, Chemitiganti R, Ghanim H, Santiago E, Haider A, Chaar N, Mok M, McKee A, Dandona P. Intranasal Insulin Administration Does Not Affect LH Concentrations in Men with Diabetes. Int J Endocrinol. 2018 Oct 31;2018:6170154. doi: 10.1155/2018/6170154. eCollection 2018.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2014
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: May 30, 2014
• First Submitted That Met QC Criteria: June 2, 2014
• First Posted (Estimate): June 3, 2014

Study Record Updates

• Last Update Posted (Actual): August 13, 2019
• Last Update Submitted That Met QC Criteria: July 23, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: hypogonadotropic hypogonadism
• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Hypogonadism; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: L14-075

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO