ObesityNCT01457703

Reproductive Hormonal Alterations in Obesity

A study testing Cetrorelix, Gonadorelin-GnRH and Recombinant LH in people with Obesity, run by University of Colorado, Denver 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

Search all trials

Trial summary

Who is it for?: Ages 18 to 40 years, women onlyHealthy volunteers can take part
Conditions the study is for: Obesity
What is being tested?: Cetrorelix, Gonadorelin-GnRH and Recombinant LH
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 62 participants
Where: 1 siteUnited States
Study dates: Jun 2010to Jul 2013
Phase: Interventional
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 18 to 40 years
Women only
Healthy volunteers accepted
Adult

Who may be able to join

Aged 18-40 at study entry
BMI either 18-25 kg/m2 or ≥30 kg/m2
prolactin (PRL) and thyroid-stimulating hormone (TSH) within normal laboratory ranges at screening
Baseline hemoglobin >11 gm/dl
History of regular menstrual cycles every 25-35 days if BMI 18-25 kg/m2
History of regular menstrual cycles every 25-40 days if BMI ≥30 kg/m2

Who cannot join

History of chronic disease affecting hormone production, metabolism or clearance
Use of medications that are known to alter or interact with reproductive hormones (e.g., thiazolidinediones, metformin)
Use of hormones within three months of enrollment
Excessive exercise (>4 hours per week)
Pregnancy, breast-feeding or current active attempts to conceive

Trial locations and contacts

1 site in 1 country.

United States1 site

Clinical Translational Research Center
Aurora, Colorado, 80045

Other trials in United States

About this study

Official title: Reproductive Hormonal Alterations in Obesity, AIMS #1 & #2

The purpose of this study is to determine why obese women have lower hormone levels and less fertility than women of normal body weight. The proposal will examine the reproductive system at the level of the brain and the ovary to define the changes that happen leading to lowered hormone production. Women will be studied throughout a menstrual cycle and given medications that will test how well their pituitary gland can make hormones that stimulate the ovary (luteinizing hormone (LH) and follicle stimulating hormone (FSH)). They will also be given a medication to abolish estrogen production in the body and their response to this medication will be assessed. Finally, the ovary's ability to produce progesterone after ovulation will be examined.

--Hypotheses:

Obese women have reduced pituitary sensitivity to exogenous gonadotropin-releasing hormone (GnRH), but normal clearance of exogenous LH. (comparative study of obese compared to normal weight women)
Obese women have abnormally increased sensitivity to estradiol negative feedback which will be reversed by an aromatase inhibitor. (comparative study of obese compared to normal weight women)

Read the detailed description

AIM 1: test the hypothesis that reduced pituitary sensitivity to GnRH-induced LH and FSH secretion causes the relative hypogonadotropic hypogonadism of obesity AIM 2: test the hypothesis that the hypothalamic-pituitary axis is abnormally sensitive to estradiol negative feedback in obesity

Conditions: Obesity
Being tested: Cetrorelix, Gonadorelin-GnRH, Recombinant LH, Letrozole
Keywords: LH pulsatility, Obesity, Reproduction
Medical subject headings: Obesity

What participants receive

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

CetrorelixDrug
Also called Cetrotide
Abolishes pituitary sensitivity to GnRH.
Gonadorelin-GnRHDrug
Also called Lutrepulse
GnRH is used to stimulate the pituitary gland to produce LH and FSH.
Recombinant LHDrug
Also called Luveris
Used to stimulate ovarian function in women.
LetrozoleDrug
Also called Femara
An aromatase inhibitor.

Study groups in NCT01457703
Study group	Role	What they receive
BMI ≥30 kg/m2	Active comparator	Group 2: * BMI ≥30 kg/m2 * History of regular menstrual cycles every 25-40 days Gonadorelin-GnRH (Lutrepulse), GnRH antagonists - Cetrorelix (Cetrotide), Recombinant LH (Luveris) were administered in Aim 1. GnRH or gonadorelin (Lutrepulse) and Letrozole were administered in Aim 2. Receives: Drug: Cetrorelix; Drug: Gonadorelin-GnRH; Drug: Recombinant LH; Drug: Letrozole
BMI 18-25 kg/m2	Experimental	* BMI 18-25 kg/m2 * History of regular menstrual cycles every 25-35 days Gonadorelin-GnRH (Lutrepulse), GnRH antagonists - Cetrorelix (Cetrotide), Recombinant LH (Luveris) were administered in Aim 1. GnRH or gonadorelin (Lutrepulse) and Letrozole were administered in Aim 2. Receives: Drug: Cetrorelix; Drug: Gonadorelin-GnRH; Drug: Recombinant LH; Drug: Letrozole

What is being measured

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

Changes in Luteinizing Hormone (LH) Pulse Amplitude (Aim 1)
Luteinizing Hormone (LH) Pulse Amplitude was measured hourly during the 12 hour study visit, and was compared between the obese and normal weight groups.
Measured: Measured hourly and averaged over the 12 hour study visit
Changes in Luteinizing Hormone (LH) Pulse Amplitude (Aim 2)
Luteinizing Hormone (LH) Pulse Amplitude was measured hourly during the 12 hour study visit, and was compared between the obese and normal weight groups.
Measured: Measured hourly and averaged over the 12 hour study visit
Changes in Pregnanediol Glucuronide (PdG) (Aim 2)
Pregnanediol glucuronide (PdG) was collected daily over the course of one menstrual cycle and averaged.
Measured: Averaged over the length of menstrual cycle

Secondary outcomes (2)

Changes in Follicle Stimulating Hormone (FSH) (Aim 1)
Follicle-stimulating hormone was measured hourly during the 12 hour study visit, and was compared between the obese and normal weight groups.
Measured: Measured hourly and averaged over the 12 hour study visit
Changes in Follicle Stimulating Hormone (FSH) (Aim 2)
Follicle-stimulating hormone was measured hourly during the 12 hour study visit, and was compared between the obese and normal weight groups.
Measured: Measured hourly and averaged over the 12 hour study visit

Timeline

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

Jun 2010Jul 2013

First posted24 Oct 2011 (estimated)
Study startJun 2010
Primary completionJul 2013
Study completionJul 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (5)Papers the sponsor has linked to this study.
Other trials for ObesityStudies of the same condition, open and under way.
More trials run by University of Colorado, DenverThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 N/A
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 62 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01457703
Sponsor's protocol ID: 09-0977
Other IDs: U54HD058155
Status last verified: Nov 2016
First submitted: 21 Sep 2011
Last updated: 12 Jan 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Jain A, Polotsky AJ, Rochester D, Berga SL, Loucks T, Zeitlian G, Gibbs K, Polotsky HN, Feng S, Isaac B, Santoro N. Pulsatile luteinizing hormone amplitude and progesterone metabolite excretion are reduced in obese women. J Clin Endocrinol Metab. 2007 Jul;92(7):2468-73. doi: 10.1210/jc.2006-2274. Epub 2007 Apr 17.
PubMed 17440019
Haynes G, Bailey MK, Davis S, Mahaffey JE. Use of methylprednisolone in epidural analgesia. Arch Neurol. 1989 Nov;46(11):1167-8. doi: 10.1001/archneur.1989.00520470017014. No abstract available.
PubMed 2818247
Rochester D, Jain A, Polotsky AJ, Polotsky H, Gibbs K, Isaac B, Zeitlian G, Hickmon C, Feng S, Santoro N. Partial recovery of luteal function after bariatric surgery in obese women. Fertil Steril. 2009 Oct;92(4):1410-1415. doi: 10.1016/j.fertnstert.2008.08.025. Epub 2008 Sep 30.
PubMed 18829008
Santen RJ, Bardin CW. Episodic luteinizing hormone secretion in man. Pulse analysis, clinical interpretation, physiologic mechanisms. J Clin Invest. 1973 Oct;52(10):2617-28. doi: 10.1172/JCI107454.
PubMed 4729055
Roth LW, Allshouse AA, Lesh J, Polotsky AJ, Santoro N. The correlation between self-reported and measured height, weight, and BMI in reproductive age women. Maturitas. 2013 Oct;76(2):185-8. doi: 10.1016/j.maturitas.2013.07.010. Epub 2013 Aug 16.
PubMed 23958434

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 12 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Reproductive Hormonal Alterations in Obesity, AIMS #1 & #2
ClinicalTrials.gov ID: NCT01457703
Acronym / sponsor ID: 09-0977
Conditions: Obesity
Keywords: LH pulsatility, Obesity, Reproduction
Study type: Interventional
Recruitment status: Completed
Enrolment: 62 participants (actual)
Lead sponsor: University of Colorado, DenverUniversity, hospital or other
Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study start: Jun 2010
Primary completion: Jul 2013 (actual)
Study completion: Jul 2013 (actual)
First posted: 24 Oct 2011 (estimated)
Results: Posted 25 Mar 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

--Hypotheses:

Obese women have reduced pituitary sensitivity to exogenous gonadotropin-releasing hormone (GnRH), but normal clearance of exogenous LH. (comparative study of obese compared to normal weight women)
Obese women have abnormally increased sensitivity to estradiol negative feedback which will be reversed by an aromatase inhibitor. (comparative study of obese compared to normal weight women)

Detailed description

Study design

Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
BMI ≥30 kg/m2	Active comparator	Drug: Cetrorelix, Drug: Gonadorelin-GnRH, Drug: Recombinant LH, Drug: LetrozoleGroup 2: * BMI ≥30 kg/m2 * History of regular menstrual cycles every 25-40 days Gonadorelin-GnRH (Lutrepulse), GnRH antagonists - Cetrorelix (Cetrotide), Recombinant LH (Luveris) were administered in Aim 1. GnRH or gonadorelin (Lutrepulse) and Letrozole were administered in Aim 2.
BMI 18-25 kg/m2	Experimental	Drug: Cetrorelix, Drug: Gonadorelin-GnRH, Drug: Recombinant LH, Drug: Letrozole* BMI 18-25 kg/m2 * History of regular menstrual cycles every 25-35 days Gonadorelin-GnRH (Lutrepulse), GnRH antagonists - Cetrorelix (Cetrotide), Recombinant LH (Luveris) were administered in Aim 1. GnRH or gonadorelin (Lutrepulse) and Letrozole were administered in Aim 2.

Who may qualify

Ages: 18 to 40 years
Sex: Female only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (6 listed)

Aged 18-40 at study entry
BMI either 18-25 kg/m2 or ≥30 kg/m2
prolactin (PRL) and thyroid-stimulating hormone (TSH) within normal laboratory ranges at screening
Baseline hemoglobin >11 gm/dl
History of regular menstrual cycles every 25-35 days if BMI 18-25 kg/m2

Key exclusion criteria (5 listed)

History of chronic disease affecting hormone production, metabolism or clearance
Use of medications that are known to alter or interact with reproductive hormones (e.g., thiazolidinediones, metformin)
Use of hormones within three months of enrollment
Excessive exercise (>4 hours per week)
Pregnancy, breast-feeding or current active attempts to conceive

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CetrorelixAlso: CetrotideAbolishes pituitary sensitivity to GnRH.	Drug	BMI 18-25 kg/m2, BMI ≥30 kg/m2
Gonadorelin-GnRHAlso: LutrepulseGnRH is used to stimulate the pituitary gland to produce LH and FSH.	Drug	BMI 18-25 kg/m2, BMI ≥30 kg/m2
Recombinant LHAlso: LuverisUsed to stimulate ovarian function in women.	Drug	BMI 18-25 kg/m2, BMI ≥30 kg/m2
LetrozoleAlso: FemaraAn aromatase inhibitor.	Drug	BMI 18-25 kg/m2, BMI ≥30 kg/m2

Primary outcome

Changes in Luteinizing Hormone (LH) Pulse Amplitude (Aim 1)
Time frame: Measured hourly and averaged over the 12 hour study visit
Luteinizing Hormone (LH) Pulse Amplitude was measured hourly during the 12 hour study visit, and was compared between the obese and normal weight groups.
Changes in Luteinizing Hormone (LH) Pulse Amplitude (Aim 2)
Time frame: Measured hourly and averaged over the 12 hour study visit
Luteinizing Hormone (LH) Pulse Amplitude was measured hourly during the 12 hour study visit, and was compared between the obese and normal weight groups.
Changes in Pregnanediol Glucuronide (PdG) (Aim 2)
Time frame: Averaged over the length of menstrual cycle
Pregnanediol glucuronide (PdG) was collected daily over the course of one menstrual cycle and averaged.

2 secondary outcomes

Changes in Follicle Stimulating Hormone (FSH) (Aim 1)
Time frame: Measured hourly and averaged over the 12 hour study visit
Changes in Follicle Stimulating Hormone (FSH) (Aim 2)
Time frame: Measured hourly and averaged over the 12 hour study visit

Results and safety

Results posted to the registry on 25 Mar 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
BMI ≥30 kg/m2	29	23
BMI 18-25 kg/m2	33	22

Primary outcome: Changes in Luteinizing Hormone (LH) Pulse Amplitude (Aim 1)

Time frame: Measured hourly and averaged over the 12 hour study visit. Mean (Inter-Quartile Range). Unit: IU/L

Measure	BMI ≥30 kg/m2 n = 10	BMI 18-25 kg/m2 n = 10
Value	4.1 (2.9 to 5.2)	3.6 (2.7 to 9.9)

Population analysed: This study was divided into two aims, and 10 obese and 10 normal weight women completed the study procedures and contributed data for analyses related to Aim 1.

Primary outcome: Changes in Luteinizing Hormone (LH) Pulse Amplitude (Aim 2)

Time frame: Measured hourly and averaged over the 12 hour study visit. Mean (Standard Deviation). Unit: IU/L

Measure	BMI ≥30 kg/m2 n = 12	BMI 18-25 kg/m2 n = 11
Value	2.21 (.32)	4.44 (1.03)

Population analysed: This study was divided into two aims, and only 12 obese and 11 normal weight women completed the study procedures for Aim 2 that allowed measure of LH pulse amplitude.

Primary outcome: Changes in Pregnanediol Glucuronide (PdG) (Aim 2)

Time frame: Averaged over the length of menstrual cycle. Mean (Standard Deviation). Unit: ug/cycle

Measure	BMI ≥30 kg/m2 n = 12	BMI 18-25 kg/m2 n = 10
Value	54.1 (33)	88.7 (64.6)

Population analysed: This study was divided into two aims, and only 12 obese and 10 normal weight women completed the urine collection study procedures for Aim 2 that allowed measure of PdG.

2 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
BMI ≥30 kg/m2	0 of 29 (0%)	0 of 29 (0%)	Not reported
BMI 18-25 kg/m2	0 of 33 (0%)	0 of 33 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 17440019Jain A, Polotsky AJ, Rochester D, Berga SL, Loucks T, Zeitlian G, Gibbs K, Polotsky HN, Feng S, Isaac B, Santoro N. Pulsatile luteinizing hormone amplitude and progesterone metabolite excretion are reduced in obese women. J Clin Endocrinol Metab. 2007 Jul;92(7):2468-73. doi: 10.1210/jc.2006-2274. Epub 2007 Apr 17.
Background: PubMed 2818247Haynes G, Bailey MK, Davis S, Mahaffey JE. Use of methylprednisolone in epidural analgesia. Arch Neurol. 1989 Nov;46(11):1167-8. doi: 10.1001/archneur.1989.00520470017014. No abstract available.
Background: PubMed 18829008Rochester D, Jain A, Polotsky AJ, Polotsky H, Gibbs K, Isaac B, Zeitlian G, Hickmon C, Feng S, Santoro N. Partial recovery of luteal function after bariatric surgery in obese women. Fertil Steril. 2009 Oct;92(4):1410-1415. doi: 10.1016/j.fertnstert.2008.08.025. Epub 2008 Sep 30.
Background: PubMed 4729055Santen RJ, Bardin CW. Episodic luteinizing hormone secretion in man. Pulse analysis, clinical interpretation, physiologic mechanisms. J Clin Invest. 1973 Oct;52(10):2617-28. doi: 10.1172/JCI107454.
Derived from this study: PubMed 23958434Roth LW, Allshouse AA, Lesh J, Polotsky AJ, Santoro N. The correlation between self-reported and measured height, weight, and BMI in reproductive age women. Maturitas. 2013 Oct;76(2):185-8. doi: 10.1016/j.maturitas.2013.07.010. Epub 2013 Aug 16.
PI Biographical dataLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Nanette Santoro, MD principal investigator

University of Colorado, Denver

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Cetrorelix, Gonadorelin-GnRH and Recombinant LH in people with Obesity, run by University of Colorado, Denver 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 5 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 12 Jan 2017. 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.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Mar 2015). 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?

Changes in Luteinizing Hormone (LH) Pulse Amplitude (Aim 1) (time frame: Measured hourly and averaged over the 12 hour study visit). The study lists 3 primary outcomes in all. 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 NCT01457703, which also lists 5 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 12 Jan 2017.