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Insulin ResistancePhase 1/2T-IRNCT01686828

T-IR- Study to Understand the Effects of Testosterone and Estrogen on the Body's Response to the Hormone Insulin

A Phase 1/2 study testing Acyline, Testosterone 1.62% gel and Letrozole in people with Insulin Resistance and Type 2 Diabetes Mellitus, run by University of Washington at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this research study is to understand the effects of testosterone and estrogen on the body's response to the hormone insulin. Read more about this study

Who is it for?
Ages 25 to 55 years, men onlyHealthy volunteers can take part
What is being tested?
Acyline, Testosterone 1.62% gel and Letrozole
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
53 participants
Where
1 siteUnited States
Study dates
Jun 2013to Dec 2017
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 25 to 55 years
  • Men only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Prostate-specific antigen (PSA) ≤ 3 ng/mL
  • Age 25-55 years
  • Ability to understand the study, study procedures and provide informed consent
  • Serum total T > 300 ng/dL
  • Normal reproductive history and exam
  • International Prostate Symptom Score (IPSS) < 11

Who cannot join

  • A history of prostate cancer including suspicious digital rectal exam (DRE) or history of highgrade prostatic intraepithelial neoplasia (PIN) on prostate biopsy
  • Invasive therapy for benign prostatic hyperplasia (BPH) in the past
  • History of acute urinary retention in the previous 3 months
  • Current or recent past use of androgenic or anti-androgenic drugs, steroids or drugs which interfere with steroid metabolism (within the last 3 months)
  • Current use of statins or glucocorticoids
  • Severe systemic illness (renal, liver, cardiac, lung disease, cancer, diabetes mellitus) or skin disease
Show all 17Show fewer
  • A history of or current breast cancer
  • Known, untreated obstructive sleep apnea
  • Hematocrit > 50 or < 34
  • Hypersensitivity to any of the drugs used in the study
  • History of a bleeding disorder or anticoagulation
  • Participation in any other drug study within past 90 days
  • History of drug or alcohol abuse within the last 12 months
  • Weight > 280 lbs. or BMI ≥ 33
  • Desire for fertility in the next 6 months or current pregnant partner
  • Sperm concentration <14 million/ml
  • Significant, uncontrolled hypertension (BP >160/100 mmHg); subjects with well-controlled BP on medical therapy will be eligible to participate

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Washington

    Seattle, Washington, 98195

Other trials in United States

About this study

Official title: Androgen-mediated Pathways in the Regulation of Insulin Sensitivity in Men

The purpose of this research study is to understand the effects of testosterone and estrogen on the body's response to the hormone insulin.

Read the detailed description

The investigators will examine the effects of testosterone on insulin sensitivity and body composition in men. This study may lend greater insight into the increased risk of diabetes evident in men with low circulating levels of testosterone. Three drugs will be used in this study: acyline, given by injection; testosterone (T) gel that is applied to the skin; and letrozole, which is an oral drug that blocks the conversion of androgens (male hormones) to estrogens (female hormones). Acyline inhibits the production of luteinizing hormone (LH) and follicle stimulating hormone (FSH). When acyline stops the production of these hormones, it blocks the signal from the brain that stimulates the testicles to make testosterone. Adding testosterone to acyline will restore physiologic levels of testosterone in some study participants. One group of men will receive T gel with letrozole, an aromatase inhibitor; these men will have normal levels of testosterone but low levels of estrogen in the blood. This design will enable determination of the respective metabolic effects of testosterone and estrogen.

Being tested
Acyline, Testosterone 1.62% gel, Letrozole, Placebo gel (for Testosterone 1.62% gel), Placebo pill (for Letrozole)
Keywords
insulin, androgens, insulin resistance, testosterone, estradiol, obesity
Medical subject headings
Insulin Resistance, Diabetes Mellitus, Type 2, Obesity, Metabolic Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AcylineDrug

    300 mcg/mL administered subcutaneously (at Day 0, Week 2)

  • Testosterone 1.62% gelDrug

    Also called Androgel

    Transdermal Testosterone Gel (either 1.25g or 5g/d) for 4 weeks

  • LetrozoleDrug

    Also called Femara

    Letrozole oral aromatase inhibitor 5mg daily for 4 weeks

  • Placebo gel (for Testosterone 1.62% gel)Drug

    placebo gel manufactured to mimic Testosterone 1.62% gel

  • Placebo pill (for Letrozole)Drug

    Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d

Study groups in NCT01686828
Study groupRoleWhat they receive
Acyline & placebo gel & placebo pillExperimentalAcyline (300mcg/kg) + placebo transdermal gel + placebo pill daily
Receives: Drug: Acyline; Drug: Placebo gel (for Testosterone 1.62% gel); Drug: Placebo pill (for Letrozole)
Acyline & Testosterone 1.25g & placebo pillExperimentalAcyline (300mcg/kg) + Testosterone gel (1.25g) daily + placebo pill daily
Receives: Drug: Acyline; Drug: Testosterone 1.62% gel; Drug: Placebo pill (for Letrozole)
Acyline & Testosterone 5g & placebo pillExperimentalAcyline (300mcg/kg) + Testosterone gel (5g) daily + placebo pill daily
Receives: Drug: Acyline; Drug: Testosterone 1.62% gel; Drug: Placebo pill (for Letrozole)
Acyline & Testosterone & LetrozoleExperimentalAcyline (300mcg/kg) + Testosterone gel (5g) daily + letrozole (5mg) daily
Receives: Drug: Acyline; Drug: Testosterone 1.62% gel; Drug: Letrozole

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Insulin Sensitivity Quantified by Matsuda Index

    Whole body insulin sensitivity as quantified by Matsuda Index at the end of the treatment period, calculated by the following equation: 10,000/square root of(FPG*FI)*(FPG+PG30*2+PG60*2+PG90*2+PG120)/8*(FPI+PI30*2+PI60*2+PI90*2+PI)/8). FPG=fasting plasma glucose level; FPI=fasting plasma insulin level; PG30,60,90, and 120=plasma glucose levels sampled at 30,60,90, and 120 minutes after oral glucose load; PI30,60,90, and 120=plasma insulin levels sampled at 30,60,90, and 120 minutes after the oral glucose load

    Measured: 4 weeks

Secondary outcomes (2)

  1. Changes in Body Composition

    Fat mass and lean mass were measured by dual energy X-ray absorptiometry (DEXA) at baseline and at the end of the 4 week treatment period

    Measured: 4 weeks

  2. Changes in Adipose Tissue Gene Expression

    We examined whether differences in lipoprotein lipase expression would be evident across study treatment groups. RNA was isolated from whole adipose tissue gene expression, and complementary DNA (cDNA) was synthesized from 1.5 ug of RNA per sample. Gene expression was measured by polymerase chain reaction (PCR) using predesigned TaqMan® Gene Expression Assays. Standard curves were included on each plate, so Ct values were converted to copy numbers of the target gene. Expression values were normalized to the geometric mean of the housekeeping genes phosphoglycerate kinase and 18s.

    Measured: 4 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Sep 2012 (estimated)
  2. Study startJun 2013
  3. Primary completionMay 2015
  4. Study completionDec 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
53 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01686828
Sponsor's protocol ID
STUDY00002641
Acronym
T-IR
Status last verified
Apr 2018
First submitted
12 Sep 2012
Last updated
8 May 2018
Data monitoring committee
Yes
Individual data sharing
Undecided

Publications

  • Flegal KM. Excess deaths associated with obesity: cause and effect. Int J Obes (Lond). 2006 Aug;30(8):1171-2. doi: 10.1038/sj.ijo.0803313. No abstract available.

    PubMed 16871273

  • Araujo AB, O'Donnell AB, Brambilla DJ, Simpson WB, Longcope C, Matsumoto AM, McKinlay JB. Prevalence and incidence of androgen deficiency in middle-aged and older men: estimates from the Massachusetts Male Aging Study. J Clin Endocrinol Metab. 2004 Dec;89(12):5920-6. doi: 10.1210/jc.2003-031719.

    PubMed 15579737

  • Yeap BB, Chubb SA, Hyde Z, Jamrozik K, Hankey GJ, Flicker L, Norman PE. Lower serum testosterone is independently associated with insulin resistance in non-diabetic older men: the Health In Men Study. Eur J Endocrinol. 2009 Oct;161(4):591-8. doi: 10.1530/EJE-09-0348. Epub 2009 Aug 6.

    PubMed 19661128

  • Muller M, Grobbee DE, den Tonkelaar I, Lamberts SW, van der Schouw YT. Endogenous sex hormones and metabolic syndrome in aging men. J Clin Endocrinol Metab. 2005 May;90(5):2618-23. doi: 10.1210/jc.2004-1158. Epub 2005 Feb 1.

    PubMed 15687322

  • Li C, Ford ES, Li B, Giles WH, Liu S. Association of testosterone and sex hormone-binding globulin with metabolic syndrome and insulin resistance in men. Diabetes Care. 2010 Jul;33(7):1618-24. doi: 10.2337/dc09-1788. Epub 2010 Apr 5.

    PubMed 20368409

  • Smith MR, Lee H, Fallon MA, Nathan DM. Adipocytokines, obesity, and insulin resistance during combined androgen blockade for prostate cancer. Urology. 2008 Feb;71(2):318-22. doi: 10.1016/j.urology.2007.08.035.

    PubMed 18308111

  • Smith MR, Lee H, Nathan DM. Insulin sensitivity during combined androgen blockade for prostate cancer. J Clin Endocrinol Metab. 2006 Apr;91(4):1305-8. doi: 10.1210/jc.2005-2507. Epub 2006 Jan 24.

    PubMed 16434464

  • Mauras N, Hayes V, Welch S, Rini A, Helgeson K, Dokler M, Veldhuis JD, Urban RJ. Testosterone deficiency in young men: marked alterations in whole body protein kinetics, strength, and adiposity. J Clin Endocrinol Metab. 1998 Jun;83(6):1886-92. doi: 10.1210/jcem.83.6.4892.

    PubMed 9626114

  • Yialamas MA, Dwyer AA, Hanley E, Lee H, Pitteloud N, Hayes FJ. Acute sex steroid withdrawal reduces insulin sensitivity in healthy men with idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2007 Nov;92(11):4254-9. doi: 10.1210/jc.2007-0454. Epub 2007 Aug 28.

    PubMed 17726076

  • Klimcakova E, Roussel B, Kovacova Z, Kovacikova M, Siklova-Vitkova M, Combes M, Hejnova J, Decaunes P, Maoret JJ, Vedral T, Viguerie N, Bourlier V, Bouloumie A, Stich V, Langin D. Macrophage gene expression is related to obesity and the metabolic syndrome in human subcutaneous fat as well as in visceral fat. Diabetologia. 2011 Apr;54(4):876-87. doi: 10.1007/s00125-010-2014-3. Epub 2011 Jan 26.

    PubMed 21267541

  • Odegaard JI, Chawla A. Mechanisms of macrophage activation in obesity-induced insulin resistance. Nat Clin Pract Endocrinol Metab. 2008 Nov;4(11):619-26. doi: 10.1038/ncpendmet0976. Epub 2008 Oct 7.

    PubMed 18838972

  • Rubinow KB, Snyder CN, Amory JK, Hoofnagle AN, Page ST. Acute testosterone deprivation reduces insulin sensitivity in men. Clin Endocrinol (Oxf). 2012 Feb;76(2):281-8. doi: 10.1111/j.1365-2265.2011.04189.x.

    PubMed 21797916

  • Ortega Martinez de Victoria E, Xu X, Koska J, Francisco AM, Scalise M, Ferrante AW Jr, Krakoff J. Macrophage content in subcutaneous adipose tissue: associations with adiposity, age, inflammatory markers, and whole-body insulin action in healthy Pima Indians. Diabetes. 2009 Feb;58(2):385-93. doi: 10.2337/db08-0536. Epub 2008 Nov 13.

    PubMed 19008342

  • Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003 Dec;112(12):1796-808. doi: 10.1172/JCI19246.

    PubMed 14679176

  • Xu HZ, Li Y, Zhao YF. [Diagnosis and treatment of osteopathic parathyroid adenoma]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2003 Nov;17(6):446-9. Chinese.

    PubMed 14663938

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Acyline, Testosterone 1.62% gel and Letrozole in people with Insulin Resistance and Type 2 Diabetes Mellitus, run by University of Washington at 1 site in United States.

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 17 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: finished, as of the sponsor's last update on 8 May 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Insulin Sensitivity Quantified by Matsuda Index (time frame: 4 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01686828, which also lists 42 linked publications.

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 8 May 2018.

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