A clinical trial of clomifene citrate in men with infertility

ISRCTN	ISRCTN16558783
DOI	https://doi.org/10.1186/ISRCTN16558783
Integrated Research Application System (IRAS)	1012496
Central Portfolio Management System (CPMS)	69132
National Institute for Health and Care Research (NIHR)	167189
Sponsor's protocol code number	CTU/2023/46
Sponsor	University College London Comprehensive Clinical Trials Unit
Funder	National Institute for Health and Care Research

Submission date: 28/02/2026
Registration date: 14/07/2026
Last edited: 14/07/2026

Recruitment status: Not yet recruiting
Overall study status: Ongoing
Condition category: Urological and Genital Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Male infertility affects many couples trying to conceive. In some men, infertility may be linked to low testosterone levels caused by problems with hormone signals that control the testes (secondary functional hypogonadism), while in others, the cause is unknown (idiopathic male infertility).

Clomifene citrate is a medication that is commonly used to treat female infertility and may help improve sperm production in men. However, more research is needed to determine how effective and safe it is for treating male infertility.

This study aims to investigate whether clomifene citrate can improve sperm concentration and fertility outcomes in men with secondary functional hypogonadism or idiopathic male infertility compared with a placebo.

Who can participate?
Men aged 18 to 44 years who have been trying to conceive for at least 12 months and have abnormal semen parameters or secondary functional hypogonadism.

What does the study involve?
A total of 160 men will take part across several NHS hospitals in the UK.

Participants will be randomly allocated to receive either:
- One 25 mg clomifene citrate tablet daily
- A placebo tablet daily

Neither participants nor the study team will know which treatment has been allocated.

Participants will take the study medication for 9 months.

They will attend follow-up visits at 3, 6, and 9 months, where they will:

Provide semen samples for analysis
Have blood tests
Have health assessments
Complete questionnaires about quality of life and sexual health

Researchers will also collect information about pregnancies and fertility treatments. A final follow-up assessment will take place 18 months after joining the study.

What are the possible benefits and risks of participating?
Participants may benefit if clomifene citrate improves sperm production and fertility outcomes. The information collected may help improve future treatment options for men with infertility.

Clomifene has a well-established safety profile but may cause mild to moderate side effects. There is also a possibility of interactions with some medications. Participants will be closely monitored throughout the study, including regular blood tests and safety reviews.

Where is the study run from?
University College London (UCL) Comprehensive Clinical Trials Unit, UK.

When is the study starting and how long is it expected to run for?
August 2026 to February 2029.

Who is funding the study?
National Institute for Health and Care Research (NIHR), UK.

Who is the main contact?
Rumana Jalil, cctu.concrete@ucl.ac.uk

Contact information

Rumana Jalil
Scientific, Public

The Comprehensive Clinical Trials Unit at UCL
90 High Holborn
London
WC1V 6LJ
United Kingdom

Phone	+44 20 3108 6584
Email	cctu.concrete@ucl.ac.uk

Dr Bassel Al Wattar
Principal investigator

90 High Holborn
London
WC1V 6LJ
United Kingdom

Phone	+44 7510311359
Email	b.wattar@nhs.net

Study information

Primary study design	Interventional
Allocation	Randomized controlled trial
Masking	Blinded (masking used)
Control	Placebo
Assignment	Single
Purpose	Treatment, Safety
Scientific title	Effectiveness of ClOmifeNe CitRate for the management of mEn wiTh infErtility (CONCRETE): A randomised double-blind placebo-controlled trial.
Study acronym	CONCRETE
Study objectives	The primary aim of CONCRETE is to evaluate the efficacy and safety of clomifene as a treatment for men with secondary hypogonadism or idiopathic male infertility compared to placebo. Secondary objective: 1. To determine the efficacy of clomifene in improving semen parameters in this group of men. 2. To determine the efficacy of clomifene in improving the reproductive outcomes in this group of men. 3. To determine the safety of clomifene as a treatment for men with secondary hypogonadism or idiopathic male infertility. 4. To explore the feasibility and acceptability of using clomifene as a primary treatment in this group of men.
Ethics approval(s)	Submitted 27/02/2026, Yorkshire & The Humber - Leeds West Research Ethics Committee (NHSBT Newcastle Blood Donor Centre, Holland Drive, Newcastle upon Tyne, NE2 4NQ, United Kingdom; -; leedswest.rec@hra.nhs.uk), ref: 26/YH/0057
Health condition(s) or problem(s) studied	Male infertility
Intervention	Patients will be randomised using the Sealed envelope platform on the computer to receive either 25mg Clomifene Citrate or a matching placebo, to be taken orally once a day for 9 months. • Experimental Arm: 25mg Clomifene Citrate • Control Arm: Placebo
Intervention type	Drug
Phase	Phase II
Drug / device / biological / vaccine name(s)	Clomifene citrate
Primary outcome measure(s)	Sperm concentration measured using semen analysis (millions per millilitre (millions/mL) at the 6-month visit
Key secondary outcome measure(s)	Sperm concentration measured using semen analysis at 3-, and 9-month visits Total sperm count as per WHO criteria measured using semen analysis at 3-, 6- and 9-month visits Percent of total sperm motility as per WHO criteria measured using semen analysis at 3-, 6- and 9-month visits Percent of progressive sperm motility as per WHO criteria measured using semen analysis at 3-, 6- and 9-month visits Percent of normal sperm morphology as per WHO criteria measured using semen analysis at 3-, 6- and 9-month visits Incidence of spontaneous clinical pregnancy measured using data collection from patient records at the 18-month visit Incidence of the need to use any Assisted Reproductive Technology (ART) treatments measured using data collection from patient records at the 18-month visit Incidence of pregnancy outcome (spontaneous or with ART) including miscarriage, stillbirth, livebirth and neonatal death measured using data collection from patient records at the 18-month visit Time to the first incidence of pregnancy from randomisation measured using data collection from patient records at the 18-month visit Incidence of the need to undergo Surgical Sperm Retrieval (SSR) procedure, the type and the outcome of the SSR procedure measured using data collection from patient records at the 18-month visit Biochemical outcomes: LH, FSH, Oestradiol, early rise total and free testosterone, oestradiol: testosterone ratio, sex hormone-binding globulin, prolactin, kidney and liver function profile measured using standard medical laboratory methods at the 3-, 6- and 9-month visits Clinical outcome: BMI (kg/m2) measured using standard methods at the 3-, 6- and 9-month visits Quality of Life outcomes measured using the Male Sexual Health Questionnaire (MSHQ) and the EQ-5D-5L questionnaire at the 3-, 6-, 9- and 18-month visits Adverse Events and Reactions (AEs/ARs) at all grades and Serious Adverse Events and Reactions (SAEs/SARs) at all grades measured using data from Case Report Forms (CRFs) at any time throughout the duration of the trial
Completion date	28/02/2029

Eligibility

Participant type(s)
Age group	Adult
Lower age limit	18 Years
Upper age limit	45 Years
Sex	Male
Target sample size at registration	160
Key inclusion criteria	1. Men assigned as biological male at birth 2. Aged ≥18-<45 years inclusive at baseline and randomisation. 3. Diagnosis of primary or secondary infertility at the time of screening, having been trying to conceive for ≥12 months with abnormal semen parameters due to: (i) reduced sperm concentration of ≤16 million spermatozoa per ml on as per the WHO criteria, or (ii) secondary functional hypogonadism (defined as early rise total testosterone ≤12pmol/l) after excluding other causes 4. Capacity to give informed consent
Key exclusion criteria	1. Primary testicular failure (confirmed with an FSH level of ≥15 IU/L) at time of screening 2. History of primary or secondary hypogonadotropic hypogonadism due to other congenital or acquired condition disturbing the hypothalamic-pituitary gonadal axis. 3. History of taking prescribed or non-prescribed hormonal treatment therapy including but not limited to clomifene, gonadotrophins, anabolic steroids and exogenous testosterone. 4. Other causes of male infertility including but not limited to; known obstructive azoospermia, untreated clinical varicocele, history of mumps orchitis, history of chemotherapy/radiotherapy treatment. 5. Abnormal karyotype, evidence of Y chromosome AZF microdeletion, cystic fibrosis gene abnormality, history of cryptorchidism
Date of first enrolment	01/08/2026
Date of final enrolment	31/07/2027

Locations

Countries of recruitment

United Kingdom
England

Study participating centres

University College London Hospital

250 Euston Road
London
NW1 2PG
England

Epsom and St Helier University Hospitals NHS Trust

St Helier Hospital
Wrythe Lane
Carshalton
SM5 1AA
England

Royal Victoria Infirmary

Queen Victoria Road
Newcastle upon Tyne
NE1 4LP
England

Southmead Hospital

Southmead Road
Westbury-on-trym
Bristol
BS10 5NB
England

St James' University Hospital

Beckett Street
Leeds
LS9 7TF
England

St Marys Hospital

Manchester Royal Infirmary
Oxford Road
Manchester
M13 9WL
England

Guy's and St Thomas' NHS Foundation Trust

Guy's Hospital, Great Maze Pond
London
SE1 9RT
England

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan	Data will be shared based on the following principles: o No data should be released that would compromise an ongoing trial or study. o There must be a strong scientific or other legitimate rationale for the data to be used for the requested purpose. o Investigators who have invested time and effort into developing a trial or study should have a period of exclusivity in which to pursue their aims with the data before key trial data are made available to other researchers. o The funder's requirements for data sharing will be adhered to. o The resources required to process requests should not be underestimated, particularly successful requests which lead to preparing data for release. Therefore, adequate resources must be available to comply in a timely manner or at all, and the scientific aims of the study must justify the use of such resources. o Data exchange complies with Information Governance and Data Security Policies in all of the relevant countries. o Data will be available for sharing after publication of the primary trial results. Researchers wishing to access CONCRETE trial data should contact the Trial Management Group, cctu.concrete@ucl.ac.uk, in the first instance.

Individual participant data (IPD) Intention to share

Yes

IPD sharing plan

Data will be shared based on the following principles:
o No data should be released that would compromise an ongoing trial or study.
o There must be a strong scientific or other legitimate rationale for the data to be used for the requested purpose.
o Investigators who have invested time and effort into developing a trial or study should have a period of exclusivity in which to pursue their aims with the data before key trial data are made available to other researchers.
o The funder's requirements for data sharing will be adhered to.
o The resources required to process requests should not be underestimated, particularly successful requests which lead to preparing data for release. Therefore, adequate resources must be available to comply in a timely manner or at all, and the scientific aims of the study must justify the use of such resources.
o Data exchange complies with Information Governance and Data Security Policies in all of the relevant countries.
o Data will be available for sharing after publication of the primary trial results. Researchers wishing to access CONCRETE trial data should contact the Trial Management Group, cctu.concrete@ucl.ac.uk, in the first instance.

Editorial Notes

30/05/2026: ISRCTN received notification of combined HRA/MHRA approval for this trial on 30/05/2026.
02/03/2026: Trial's existence confirmed by NHS HRA.