Reproductive Hormones During Sustained Administration of Kisspeptin

Study Overview
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Brief Summary
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We want to find out what happens to reproductive hormone levels; Luteinising Hormone (LH), Follicle Stimulating Hormone (FSH), testosterone and oestradiol when kisspeptin is administered to people for a period of 8 days each month, using either placebo (saline) or kisspeptin in doses of 0.1, 0.3 or 1.0 nmol/kg/hour.

Detailed Description
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Participants will be invited to have an initial baseline study to look at the hormone levels at regular intervals over the course of a day (8hours). Following this, on a different day, volunteers will have an infusion of kisspeptin, which will be administered by a small pump to deliver the hormone into subcutaneous tissue (fatty tissue just below the skin surface). On day 1 of the pump infusion there will be another day of regular blood sampling for 8 hours. After this the kisspeptin pump will continue and the participants will return to the research unit on day 3 for a review and a single blood test. On day 5 the participants will have a review, a blood test and the kisspeptin pump will be changed. Kisspeptin infusion will continue and on Day 8 the participant will return for another 8 hour study. At the end of this the kisspeptin pump will be removed. The above will be repeated using either placebo (saline) or kisspeptin in doses of 0.1, 0.3 or 1.0 nmol/kg/hour during the early follicular phase of 4 separate menstrual cycles.

Official Title
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The Physiological Changes in Reproductive Hormones During Sustained Administration of Kisspeptin in Humans.

Conditions
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Hypothalamic Dysfunction, Fertility Disorders

Intervention / Treatment
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* Other: Kisspeptin 0.1
* Other: Saline
* Other: Kisspeptin 0.3
* Other: Kisspeptin 1.0


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Aged 18-60 years old Ability to give informed consent Secondary hypogonadism (or healthy participant) Exclusion criteria: anaemia medical problems such as severe heart, kidney or liver disease blood donation in the last three months or intention to donate blood within 3 months of the end of the study needle phobia Poor venous access Active psychiatric illness Severe allergies Impaired ability to provide full consent to take part in the study Current alcohol or illicit drug dependence Current pregnancy or breast feeding Plans to conceive within 3 months of starting the study (barrier contraception must be used during and for 3 months after the end of the study) Arthritis or any impairment of hand coordination which would preclude using a hormone pump

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This is a prospective, single-blinded placebo-controlled study. Women will receive an 8-h SC infusion of kisspeptin-54 0·1, 0·3 or 1·0 nmol/kg/h or saline in the early follicular phase of 4 separate menstrual cycles. Luteinising Hormone (LH), Follicle stimulating hormone (FSH) and oestradiol will be measured every 10 min during the infusions.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Kisspeptin 0.1<br>Participants will receive kisspeptin hormone at a dose rate of 0.1nmol/kg/hour via a subcutaneous pump device for 8 days during the early follicular phase of their menstrual cycle. | Other: Kisspeptin 0.1<br>* Participants will receive kisspeptin hormone at a dose rate of 0.1nmol/kg/hour via a subcutaneous pump device for 8 days during the early follicular phase of their menstrual cycle. LH, FSH and oestradiol will be measured on day 1 and 8, at 10minute intervals for 8 hours and on Days 3 and 5 they will have a single blood measurement of the same hormones.<br>|
| Placebo Comparator: Saline<br>Participants will receive placebo (saline) via a subcutaneous pump device for 8 days during the early follicular phase of their menstrual cycle. | Other: Saline<br>* Participants will receive placebo (saline) via a subcutaneous pump device for 8 days during the early follicular phase of their menstrual cycle. LH, FSH and oestradiol will be measured on day 1 and 8, at 10minute intervals for 8 hours and on Days 3 and 5 they will have a single blood measurement of the same hormones.<br>|
| Active Comparator: Kisspeptin 0.3<br>Participants will receive kisspeptin hormone at a dose rate of 0.3nmol/kg/hour via a subcutaneous pump device for 8 days during the early follicular phase of their menstrual cycle. | Other: Kisspeptin 0.3<br>* Participants will receive kisspeptin hormone at a dose rate of 0.3 nmol/kg/hour via a subcutaneous pump device for 8 days during the early follicular phase of their menstrual cycle. LH, FSH and oestradiol will be measured on day 1 and 8, at 10minute intervals for 8 hours and on Days 3 and 5 they will have a single blood measurement of the same hormones.<br>|
| Active Comparator: Kisspeptin 1.0<br>Participants will receive kisspeptin hormone at a dose rate of 1.0nmol/kg/hour via a subcutaneous pump device for 8 days during the early follicular phase of their menstrual cycle. | Other: Kisspeptin 1.0<br>* Participants will receive kisspeptin hormone at a dose rate of 1.0 nmol/kg/hour via a subcutaneous pump device for 8 days during the early follicular phase of their menstrual cycle. LH, FSH and oestradiol will be measured on day 1 and 8, at 10minute intervals for 8 hours and on Days 3 and 5 they will have a single blood measurement of the same hormones.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of Kisspeptin on hypothalamic reproductive function - LH levels | Luteinising hormone levels will be measured at various time-points to assess the effect of kisspeptin on hypothalamic reproductive function, whilst the participant receives a kisspeptin infusion | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of Kisspeptin on hypothalamic reproductive function - FSH levels | FSH levels will be measured at various time-points to assess the effect of kisspeptin on hypothalamic reproductive function, whilst the participant receives a kisspeptin infusion | 3 months | 
| Effect of Kisspeptin on hypothalamic reproductive function - Oestradiol levels | Oestradiol levels will be measured at various time-points to assess the effect of kisspeptin on hypothalamic reproductive function, whilst the participant receives a kisspeptin infusion | 3 months | 
| Do participants with normal fertility respond differently to sustained administration of kisspeptin, compared to participants with reduced fertility? | Reproductive hormone levels (LH, FSH, oestradiol) will be measured at various timepoints, whilst the participant receives a kisspeptin infusion. The results of the two groups will then be compared with one another. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infertility, Kisspeptin, Reproductive hormones