Reproductive Hormones During Sustained Administration of Kisspeptin

Official title

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

Overview

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.

Interventions

• Other Kisspeptin 0.1
  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.
• Other Saline
  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.
• Other Kisspeptin 0.3
  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.
• Other Kisspeptin 1.0
  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.

Primary outcome measures

• Effect of Kisspeptin on hypothalamic reproductive function - LH levels [Time frame: 3 months]

Secondary outcome measures (3)

• Effect of Kisspeptin on hypothalamic reproductive function - FSH levels [Time frame: 3 months]
• Effect of Kisspeptin on hypothalamic reproductive function - Oestradiol levels [Time frame: 3 months]
• Do participants with normal fertility respond differently to sustained administration of kisspeptin, compared to participants with reduced fertility? [Time frame: 3 months]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Crossover

Masking

Single blind

Primary purpose

Treatment

Study locations

United Kingdom · 1 center

• Imperial College NHS Healthcare Trust — London

Publications

• 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. PMID 16174713
• 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. PMID 17635940
• 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: 10.1 PMID 19820030
• 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. PMID 20980998
• 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. PMID 21976724

Identifiers

NCT: NCT02081924 · 13/LO/1807

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗