Investigating the role of nitric oxide on reproductive hormones in humans
| ISRCTN | ISRCTN68237998 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN68237998 |
| IRAS number | 343389 |
| Secondary identifying numbers | Protocol number: 172999, CPMS 65432 |
- Submission date
- 21/05/2025
- Registration date
- 29/05/2025
- Last edited
- 29/05/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English summary of protocol
Background and study aims
This study is looking at how a molecule called nitric oxide (NO) affects fertility. Fertility is controlled by hormones in the brain, especially one called GnRH, which helps trigger the release of other important reproductive hormones. Another hormone, kisspeptin, also plays a key role in fertility and has been safely used to boost hormone levels in both men and women.
Early research suggests that nitric oxide might help regulate these hormones and could even work together with kisspeptin. However, we don’t yet know how nitric oxide affects hormone levels in people. This study aims to find out how nitric oxide influences reproductive hormones, both on its own and when combined with kisspeptin or GnRH. The goal is to improve how we diagnose and treat fertility problems.
Who can participate?
The study is open to adults aged 18 and over. There are two groups:
Group A: People with normal fertility. Women must have regular periods, and men must not have signs of low testosterone or fertility issues.
Group B: People with reduced fertility. Women may have irregular or no periods, and men may have low testosterone or fertility problems.
What does the study involve?
If you’re interested, you’ll first fill out a short questionnaire. If you’re suitable, you’ll be invited to a screening visit at Charing Cross Hospital. This includes a physical exam, blood tests, heart check (ECG), and a chance to ask questions.
If you’re eligible, you’ll attend six study visits, each lasting 5–8 hours and spaced at least two days apart. During these visits, you’ll receive different combinations of treatments—some may include nitric oxide (via a patch), kisspeptin, GnRH, or a placebo. Neither you nor the researchers will know which treatment you’re getting at each visit.
Some participants may be asked to attend three extra visits using a different nitric oxide medication (like sildenafil tablets). Each visit will include blood tests, mood questionnaires, and checks on your heart rate and blood pressure. Women will also take a pregnancy test before each visit.
What are the possible benefits and risks of participating?
You may not benefit directly, but your participation will help researchers better understand how nitric oxide affects fertility. This could lead to better treatments in the future. Some blood tests might also reveal useful health information, which can be shared with your GP if you agree.
Where is the study run from?
Imperial College London, UK
When is the study starting and how long is it expected to run for?
July 2025 to July 2029
Who is funding the study?
NIHR Biomedical Research Centre at Imperial College London (UK)
Who is the main contact?
Professor Waljit Dhillo
Dr Ali Abbara
Dr Jovanna Tsoutsouki
The team can be contacted at imperial.kisspeptin@nhs.net
Contact information
Scientific, Principal Investigator
6th Floor Commonwealth Building
Imperial College London
Hammersmith Campus
Du Cane Road
London
W12 0NN
United Kingdom
 ORCID ID |
0000-0001-5950-4316 |
|---|---|
| Phone | +44 (0)207 594 3487 |
| w.dhillo@imperial.ac.uk |
Public
6th Floor Commonwealth Building
Imperial College London
Hammersmith Campus
Du Cane Road
London
W12 0NN
United Kingdom
| ORCID ID |
0000-0001-5496-2393 |
|---|---|
| Phone | +44 (0)207 594 3487 |
| jt722@ic.ac.uk |
Scientific, Principal Investigator
6th Floor Commonwealth Building
Imperial College London
Hammersmith Campus
Du Cane Road
London
W12 0NN
United Kingdom
| ORCID ID |
0000-0003-2795-5256 |
|---|---|
| Phone | +44 (0)207 594 3487 |
| ali.abbara@imperial.ac.uk |
Study information
| Study design | Randomized double-blind placebo-controlled crossover study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | University/medical school/dental school |
| Study type | Other |
| Participant information sheet | 47376 PIS+Normal+Fertility v3 07Jan25.pdf |
| Scientific title | The physiological role of nitric oxide on reproductive hormones in humans |
| Study acronym | NO study |
| Study objectives | Nitric oxide is implicated in hypothalamic reproductive function and reproductive hormone responses may alter in the presence of a nitric oxide donor or nitric oxide enhancer. |
| Ethics approval(s) |
Approved 21/01/2025, East of England - Cambridgeshire and Hertfordshire Research Ethics Committee (2 Redman Place, London, EC20 1JQ, United Kingdom; +44 2071048096; cambsandherts.rec@hra.nhs.uk), ref: 24/EE/0254 |
| Health condition(s) or problem(s) studied | The role of nitric oxide on reproductive hormone responses in healthy individuals and individuals with reproductive disorders. |
| Intervention | Participants will attend six study visits in a balanced random order, each involving administration of one of the following intervention combinations: A nitric oxide (NO) enhancer/donor (administered as a transdermal patch or oral tablet) and intravenous placebo. Placebo administered both as a patch or tablet and intravenously. Intravenous bolus kisspeptin and placebo (patch or tablet). Intravenous bolus gonadotropin-releasing hormone (GnRH) and placebo (patch or tablet). Intravenous bolus GnRH and a nitric oxide (NO) enhancer/donor (patch or tablet). Intravenous bolus kisspeptin and a nitric oxide (NO) enhancer/donor (patch or tablet). Kisspeptin will be administered as an intravenous bolus at a dose of up to 25.6 nmol/kg. GnRH will be administered as an intravenous bolus at a dose of 100 micrograms. The NO enhancer/donor will be delivered either as a transdermal patch (up to 0.8 mg/hour nitroglycerin) or as an oral tablet (e.g. sildenafil 50 mg), depending on the study arm. Placebo treatments will be identical in appearance, formulation, and route of administration to their active counterparts to maintain blinding. The randomisation sequence will be generated using simple randomisation by an independent statistician prior to the start of recruitment. Participants will be allocated a unique study ID in sequential order upon enrolment. The randomisation schedule will be held centrally at Imperial College London and concealed from investigators responsible for drug administration. All participants, research nurses, and study doctors will be blinded to treatment allocation. The primary outcome will be changes in reproductive hormone levels following each intervention combination. |
| Intervention type | Biological/Vaccine |
| Pharmaceutical study type(s) | Physiological study using a multi-method approach: physiological, behavioural and hormonal analyses. |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Kisspeptin, Gonadotropin Releasing Hormone, Nitric Oxide donor (Nitroglycerine patch) or Nitric Oxide enhancer tablet (Sildenafil) |
| Primary outcome measure | Change in kisspeptin-stimulated luteinising hormone (LH) levels in the presence of a nitric oxide donor/enhancer, measured using blood samples collected at baseline and every 10 minutes for up to 480 minutes during each of six study visits, and analysed using established laboratory techniques. |
| Secondary outcome measures | 1. Change in kisspeptin-stimulated blood parameters, including follicle-stimulating hormone (FSH), oestradiol, progesterone, and testosterone, in the presence of a nitric oxide donor/enhancer, measured using blood samples collected at baseline and at regular intervals (at a minimum every 10 minutes) for up to 480 minutes during each of six study visits, and analysed using established laboratory techniques 2. Change in Gonadotrophin Releasing Hormone (GnRH)-stimulated blood parameters, including LH, FSH, oestradiol, progesterone, and testosterone, in the presence of a nitric oxide donor/enhancer, measured using blood samples collected at baseline and at regular intervals (at a minimum every 10 minutes) for up to 480 minutes during each of six study visits, and analysed using established laboratory techniques 3. Safety assessments, including a) Adverse events, monitored continuously throughout each of the six study visits; b) Blood pressure and heart rate, measured using standard clinical methods at the beginning of each study visit, at regular intervals during the visit, and at the end of the visit |
| Overall study start date | 01/08/2024 |
| Completion date | 03/08/2030 |
Eligibility
| Participant type(s) | Healthy volunteer, Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 100 Years |
| Sex | Both |
| Target number of participants | 40 |
| Key inclusion criteria | GROUP A: PEOPLE WITH NORMAL REPRODUCTIVE FUNCTION: 1. Aged 18 years to 35 years 2. Ability to give informed consent GROUP B: PEOPLE WITH REDUCED REPRODUCTIVE FUNCTION: 1. Aged 18 years or older 2. Ability to give informed consent |
| Key exclusion criteria | GROUP A: PEOPLE WITH NORMAL REPRODUCTIVE FUNCTION: 1. Medical or psychological conditions that would impair their ability to participate reliably in the study or give informed consent. 2. History of any medical, psychological or other condition, or use of any medications, including over-the-counter products, which, in the opinion of the investigators, would either interfere with the study or potentially cause harm to the volunteer. 3. Severe allergies, or allergy specific to Sildenafil, Nitroglycerine or other ingredients of the patch/medication 4. Significant anaemia (Hb<11 g/dl) 5. Pregnancy 6. Participation in any research study within the preceding 2 weeks GROUP B: PEOPLE WITH REDUCED REPRODUCTIVE FUNCTION: 1. Medical or psychological conditions that would impair their ability to participate reliably in the study or give informed consent. 2. History of any medical, psychological or other condition, or use of any medications, including over-the-counter products, which, in the opinion of the investigators, would either interfere with the study or potentially cause harm to the volunteer. 3. Severe allergies, or allergy specific to Sildenafil, Nitroglycerine or other ingredients of the patch/medication 4. Significant anaemia (Hb<11 g/dl) 5. Pregnancy 6. Participation in any research study within the preceding 2 weeks |
| Date of first enrolment | 21/07/2025 |
| Date of final enrolment | 21/07/2028 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
London
W6 8RP
United Kingdom
Sponsor information
University/education
Research Governance and Integrity Team
Room 215, Level 2
Medical School Building
Norfolk Place
London
W2 1PG
England
United Kingdom
| Phone | +44 (0)207 594 9459 |
|---|---|
| cheuk-fung.wong@imperial.ac.uk | |
| Website | https://www.imperial.ac.uk |
"ROR" |
https://ror.org/041kmwe10 |
Funders
Funder type
Government
Private sector organisation / Research institutes and centers
- Alternative name(s)
- NIHR Imperial BRC, Imperial Biomedical Research Centre, BRC
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 21/07/2029 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Published as a supplement to the results publication |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal and presentation at national/international scientific conferences. |
| IPD sharing plan | All data generated or analysed during this study will be included in the subsequent results publication. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version 3 | 07/01/2025 | 29/05/2025 | No | Yes |
| Participant information sheet | version 3 | 07/01/2025 | 29/05/2025 | No | Yes |
Additional files
Editorial Notes
21/05/2025: Trial's existence confirmed by East of England - Cambridgeshire and Hertfordshire Research Ethics Committee.
