Clinical studies to examine the effects of intranasal kisspeptin delivery on reproductive hormones

ISRCTN	ISRCTN10095215
DOI	https://doi.org/10.1186/ISRCTN10095215
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	Nil known
Integrated Research Application System (IRAS)	232585
Protocol serial number	Protocol version 4, IRAS 232585
Sponsor	Imperial College London
Funders	Medical Research Council, National Institute for Health Research

Submission date: 08/03/2022
Registration date: 09/03/2022
Last edited: 22/08/2025

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims:
Kisspeptin is a hormone which acts as the master regulator of reproductive hormone release in humans. Clinical studies demonstrate that intravenous (into a vein) or subcutaneous (under the skin) kisspeptin administration could be used to treat reproductive disorders. A non-invasive delivery route would be preferable to patients and clinicians. To address this, the aim of this study is to find out whether intranasal administration (snorting) of kisspeptin can stimulate reproductive hormone release in healthy volunteers and patients with reproductive disorders.

Who can participate?
Healthy men and women and patients with reproductive disorders, aged 18 – 70 years

What does the study involve?
Participants will attend at least two study visits at least 1 week apart at the Clinical Research Unit (Charing Cross Hospital, London). At one visit kisspeptin will be self-administered using a nasal spray device and at the other visit a placebo (dummy drug) will be used instead. Blood samples will be collected through a cannula (tube) every 15 minutes for 4 hours to measure reproductive hormone release.

What are the possible benefits and risks of participating?
Kisspeptin is a naturally occurring hormone which has been given to over 500 men and women without complications or side effects. The main benefit will be to help develop a future treatment for patients with reproductive disorders.

When is the study starting and how long is it expected to run for?
June 2017 to April 2024

Who is funding the study?
1. Medical Research Council (MRC) (UK)
2. National Institute for Health Research (NIHR) (UK)

Who is the main contact?
Dr Edouard Mills
imperial.kisspeptin@nhs.net

Contact information

Dr Edouard Mills
Public

6th Floor Commonwealth Building
Imperial College London
Hammersmith Campus
Du Cane Road
London
W12 0NN
United Kingdom

Phone	+44 (0)207 594 3487
Email	imperial.kisspeptin@nhs.net

Prof Waljit Dhillo
Principal investigator

6th Floor Commonwealth Building
Imperial College London
Hammersmith Campus
Du Cane Road
London
W12 0NN
United Kingdom

Phone	+44 (0)207 594 3487
Email	imperial.kisspeptin@nhs.net

Study information

Primary study design	Interventional
Study design	Randomized placebo-controlled cross-over study
Secondary study design	Randomised cross over trial
Participant information sheet	41319_PIS_27Jan20_V5.pdf
Scientific title	Investigating the effects of intranasal kisspeptin administration on reproductive hormone secretion
Study objectives	Intranasal kisspeptin administration stimulates reproductive hormone secretion in healthy volunteers and patients with common reproductive disorders.
Ethics approval(s)	Approved 12/10/2017, London Riverside Research Ethics Committee (Chelsea & Westminster Hospital, 369 Fulham Road, London, SW10 9NH, UK; +44 (0)20 7104 8112; riverside.rec@hra.nhs.uk), REC ref: 17/LO/1504
Health condition(s) or problem(s) studied	Reproductive disorders
Intervention	Randomised, placebo-controlled, cross-over study in healthy volunteers (men and women) and patients with common reproductive disorders (including hypothalamic amenorrhoea). Following self-administration of intranasal kisspeptin (dose range 3.2 to 25.6 nmol/kg) or placebo using a nasal spray device, serum reproductive hormones are measured every 15 minutes for 4 hours. Study visits will be at least 1 week apart to ensure washout, with the order of the interventions randomised (using https://www.randomizer.org).
Intervention type	Drug
Phase	Phase I
Drug / device / biological / vaccine name(s)	Kisspeptin-54
Primary outcome measure(s)	Blood levels of reproductive hormones (kisspeptin, luteinizing hormone, follicle stimulating hormone, testosterone [men] and oestradiol/progesterone [women]) measured using automated chemiluminescent immunoassays at baseline and every 15 minutes for 4 hours
Key secondary outcome measure(s)	1. Safety monitoring: heart rate, blood pressure, and the presence of adverse symptoms measured using automated blood pressure monitor every 15 minutes for 4 hours 2. Behavioural parameters of reproductive behaviour assessed using validated psychometric questionnaires (including the Sexual Arousal and Desire Inventory, Positive and Negative Affect Schedule, and State-Trait-Anxiety-Inventory) at baseline and every hour until 4 hours
Completion date	01/04/2024

Eligibility

Participant type(s)	Mixed
Age group	Adult
Lower age limit	18 Years
Upper age limit	70 Years
Sex	All
Target sample size at registration	18
Total final enrolment	34
Key inclusion criteria	Healthy volunteers: 1. Aged 18–70 years 2. Non-smokers 3. Free of current or past physical or psychiatric illness 4. Naive to psychoactive substances, prescribed or illicit, for a minimum of 6 months prior to screening. 5. Regular menstrual cycles (women) For patients with common reproductive disorders: 1. Patients diagnosed in accordance with established guidelines (e.g. Endocrine Society guidelines for hypothalamic amenorrhoea)
Key exclusion criteria	1. History of any medical, psychological or other condition, or use of any medications, including over-the-counter products and hormonal therapies, which, in the opinion of the investigators, would either interfere with the study or potentially cause harm to the participant 2. Medical or psychological conditions that would impair their ability to participate reliably in the study or give informed consent 3. Pregnancy and/or breastfeeding 4. Without access at home to a telephone, or other factor likely to interfere with ability to participate reliably in the study 5. History of hypersensitivity to any of the components administered 6. Treatment with an investigational drug within the preceding 2 months 7. Those who have or intend to donate blood or blood products within three months before or following study completion 8. A history of major haematological, renal, thyroid or hepatic abnormalities or significant cardiovascular disease 9. A history of cancer
Date of first enrolment	14/01/2020
Date of final enrolment	01/12/2023

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Imperial College London

Clinical Research Unit
Charing Cross Hospital
Fulham Palace Rd
London
W6 8RF
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Other
IPD sharing plan	Restrictions apply to the availability of some or all data generated or analyzed during this study to preserve patient confidentiality. The team will on request detail the restrictions and any conditions under which access to some data may be provided. Please contact Prof. Waljit Dhillo (w.dhillo@imperial.ac.uk). The data will only become available once the study has been completed and will be at the discretion of the PI. Most data will not be available due to participant confidentiality.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article		10/04/2025	22/08/2025	Yes	No
HRA research summary			28/06/2023	No	No
Participant information sheet	version 5	27/01/2020	09/03/2022	No	Yes
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Additional files

41319_PIS_27Jan20_V5.pdf: Participant information sheet

Editorial Notes

22/08/2025: Publication reference and total final enrolment added.
28/07/2023: Participant recruitment for the patient arm of this study commenced on 03/05/2022.
13/12/2022: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/12/2022 to 01/12/2023.
2. The overall trial end date was changed from 01/04/2023 to 01/04/2024.
3. The intention to publish date was changed from 01/08/2023 to 01/08/2024.
09/03/2022: Trial's existence confirmed by the London Riverside Research Ethics Committee.