Reproductive Hormones During Sustained Administration of Kisspeptin (KisspeptPump)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Fertility Disorders; Hypothalamic Dysfunction
• Intervention / Treatment: Other: Kisspeptin 0.1; Other: Saline; Other: Kisspeptin 0.3; Other: Kisspeptin 1.0

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.

• Study Type: Interventional
• Enrollment (Anticipated): 76
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: ALi Abbara, PhD MRCP; Phone Number: 020 8383 3242; Email: ali.abbara@imperial.ac.uk
• Study Contact Backup: Name: Debbie A Papadopoulou, BSc MRes; Phone Number: 020 8383 3242; Email: d.papadopoulou@imperial.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom, W12 0NN
    • Recruiting
    • Imperial College NHS Healthcare Trust
    • Contact: Waljit Dhillo, PhD, FRCP; Phone Number: 020 8383 3242; Email: w.dhillo@imperial.ac.uk
    • Contact: Channa Jayasena, MBBS, PhD; Phone Number: 020 8383 3242; Email: c.jayasena@imperial.ac.uk
    • Principal Investigator: Waljit Dhillo, PhD, FRCP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	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.
Placebo Comparator: Saline; Participants will receive placebo (saline) via a subcutaneous pump device for 8 days during the early follicular phase of their menstrual cycle.	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.
Active Comparator: Kisspeptin 0.3; 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; 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.
Active Comparator: Kisspeptin 1.0; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Imperial College London
• Investigators: Principal Investigator: Waljit Dhillo, PhD, FRCP, Imperial College London

Publications and helpful links

General 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2014
• Primary Completion (Anticipated): November 30, 2027
• Study Completion (Anticipated): November 30, 2027

Study Registration Dates

• First Submitted: February 26, 2014
• First Submitted That Met QC Criteria: March 5, 2014
• First Posted (Estimate): March 7, 2014

Study Record Updates

• Last Update Posted (Actual): March 15, 2023
• Last Update Submitted That Met QC Criteria: March 14, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Infertility; Kisspeptin; Reproductive hormones
• Other Study ID Numbers: 13/LO/1807

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No