Clinical trial NCT02081924: Reproductive Hormones During Sustained Administration of Kisspeptin
Official title: The Physiological Changes in Reproductive Hormones During Sustained Administration of Kisspeptin in Humans.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Fertility Disorders
Hypothalamic Dysfunction
Keywords: Infertility
Kisspeptin
Reproductive hormones
Lead sponsor: Imperial College London
Sponsor class: OTHER
First posted: 2014-03-07
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Effect of Kisspeptin on hypothalamic reproductive function - LH levels
timeFrame: 3 months
Secondary outcomes:
measure: Effect of Kisspeptin on hypothalamic reproductive function - FSH levels
timeFrame: 3 months
measure: Effect of Kisspeptin on hypothalamic reproductive function - Oestradiol levels
timeFrame: 3 months
measure: Do participants with normal fertility respond differently to sustained administration of kisspeptin, compared to participants with reduced fertility?
timeFrame: 3 months
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Imperial College NHS Healthcare Trust
Study officials:
affiliation: Imperial College London
name: Waljit Dhillo, PhD, FRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dhillo WS, Chaudhri OB, Patterson M, Thompson EL, Murphy KG, Badman MK, McGowan BM, Amber V, Patel S, Ghatei MA, Bloom SR. Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males. J Clin Endocrinol Metab. 2005 Dec;90(12):6609-15. doi: 10.1210/jc.2005-1468. Epub 2005 Sep 20.
citation: Dhillo WS, Chaudhri OB, Thompson EL, Murphy KG, Patterson M, Ramachandran R, Nijher GK, Amber V, Kokkinos A, Donaldson M, Ghatei MA, Bloom SR. Kisspeptin-54 stimulates gonadotropin release most potently during the preovulatory phase of the menstrual cycle in women. J Clin Endocrinol Metab. 2007 Oct;92(10):3958-66. doi: 10.1210/jc.2007-1116. Epub 2007 Jul 17.
citation: Jayasena CN, Nijher GM, Chaudhri OB, Murphy KG, Ranger A, Lim A, Patel D, Mehta A, Todd C, Ramachandran R, Salem V, Stamp GW, Donaldson M, Ghatei MA, Bloom SR, Dhillo WS. Subcutaneous injection of kisspeptin-54 acutely stimulates gonadotropin secretion in women with hypothalamic amenorrhea, but chronic administration causes tachyphylaxis. J Clin Endocrinol Metab. 2009 Nov;94(11):4315-23. doi: 10.1210/jc.2009-0406. Epub 2009 Oct 9.
citation: Jayasena CN, Nijher GM, Abbara A, Murphy KG, Lim A, Patel D, Mehta A, Todd C, Donaldson M, Trew GH, Ghatei MA, Bloom SR, Dhillo WS. Twice-weekly administration of kisspeptin-54 for 8 weeks stimulates release of reproductive hormones in women with hypothalamic amenorrhea. Clin Pharmacol Ther. 2010 Dec;88(6):840-7. doi: 10.1038/clpt.2010.204. Epub 2010 Oct 27.
citation: Jayasena CN, Nijher GM, Comninos AN, Abbara A, Januszewki A, Vaal ML, Sriskandarajah L, Murphy KG, Farzad Z, Ghatei MA, Bloom SR, Dhillo WS. The effects of kisspeptin-10 on reproductive hormone release show sexual dimorphism in humans. J Clin Endocrinol Metab. 2011 Dec;96(12):E1963-72. doi: 10.1210/jc.2011-1408. Epub 2011 Oct 5.