Condition category
Pregnancy and Childbirth
Date applied
15/07/2019
Date assigned
05/09/2019
Last edited
05/09/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

Plain English Summary

Background and study aims
Many couples experience miscarriage, but 1 in 100 couples in the UK experience recurrent miscarriage (defined as three or more miscarriages), which often has no explanation or available treatment. One reason for the lack of explanation is our neglect of detailed examination of the male partner, particularly the causes and effects of sperm with damaged DNA. One reason for the lack of explanation is our neglect of detailed examination of the male partner, particularly the causes and effects of sperm with damaged DNA.
We propose to test the effects of a combined vitamin and mineral supplement in a pilot trial on 30 men with poor sperm DNA quality in our recurrent miscarriage population. We have worked with one of Europe’s leading producers of nutritional supplements to design the supplement formulation according to the latest evidence. As the process by which sperm are made takes around 70 days the men will be asked to take the supplement for at least three months with monitoring during this time of sperm DNA quality. While the men are on the supplement and in the successive three months we will also monitor whether the medication increases the chance of a natural pregnancy and whether this pregnancy goes to term. As all components are available to individuals via many different supplements we see no reason to insist that the couples take contraceptive precautions during the pilot trial.
This trial pilot topic was selected after extensive engagement with our patient population, and the study has been designed with their guidance.

Who can participate?
Couples who have had two or more miscarriages in the past

What does the study involve?
The purpose of this study is to test whether a large clinical trial of giving men a specially formulated food supplement ‘vitamin pill’ is feasible. Participation in our study is entirely voluntary. To make sure the test is fair, participants are split into two groups and neither researchers nor the participants know which group participants are in. The active treatment group take a pill that contains a series of vitamins and minerals that we have specifically chosen to help the DNA in sperm pack better and be less likely to be damaged. This formulation is not available commercially, so it is not available in a pharmacy or online. All ingredients in the pill are common and routinely recommended as part of a healthy diet. People in the control group take a dummy treatment, which looks identical to active pill, called a placebo. Trials have placebo groups to give us a baseline that we can compare to and see if the treatment has any effect. Participants cannot request to be placed in either group. Participants will provide semen and blood samples for analysis three times in the trial and keep a food diary

What are the possible benefits and risks of participating?
At the moment there is not enough evidence to say whether the trial supplement is beneficial. Minor side-effects of any food supplementation can include an upset stomach, but this is rare. All of the ingredients in our supplement are known to be safe and are common in food.

Where is the study run from?
Tommy's National Miscarriage Centre, Birmingham Women's Hospital, UK

When is the study starting and how long is it expected to run for?
December 2019 to December 2021.

Who is funding the study?
1. National Institute for Health Research (NIHR)
2. Bayer HealthCare

Who is the main contact?
Dr Jackson Kirkman-Brown
patomium@trials.bham.ac.uk

Trial website

http://www.birmingham.ac.uk/patomium

Contact information

Type

Scientific

Primary contact

Dr Jackson Kirkman-Brown

ORCID ID

http://orcid.org/0000-0003-2833-8970

Contact details

Centre for Human Reproductive Science
Institute for Biomedical Research
Vincent Drive
Edgbaston
The University of Birmingham
Birmingham
B15 2TG
United Kingdom
+44 121 414 5867
j.kirkmanbrown@bham.ac.uk

Additional identifiers

EudraCT number

2019-000315-91

ClinicalTrials.gov number

Nil known

Protocol/serial number

42663

Study information

Scientific title

The pAToMiUM trial - pilot Antioxidant Therapy of Men in Unexplained Miscarriage

Acronym

pAToMiUM

Study hypothesis

Using a minerals and antioxidants dietary supplementation may improve sperm DNA quality, in turn resulting in better reproductive outcomes. This blinded randomised controlled pilot study will assess feasibility of a full-scale trial.

Ethics approval

Approval pending, East Midlands - Derby Research Ethics Committee (Riverside Centre (Derwent Room), Pride Park, Derby, Riverside Court, Pride Park, Derby, DE24 8HY; +442071048036; NRESCommittee.eastmidlands-derby@nhs.net), ref: 19/EM/0208

Study design

Randomised; Both; Design type: Treatment, Screening, Drug, Physical, Active Monitoring, Validation of investigation /therapeutic procedures

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Miscarriage, elevated sperm DNA fragmentation

Intervention

Menevit is a daily food grade dietary supplementation (oral single-tablet combined vitamin, antioxidant and mineral dietary supplement) designed for men considering conception by BAYER Consumer Health, which will be tested in this double-blinded, placebo-controlled pilot trial.

Participants will be screened into the trial via having elevated sperm DNA fragmentation as measured by the TUNEL assay. Men that are eligible for the study will be randomised to take this supplement or matched placebo.

Men will take the single tablet once daily for 6 months and will provide a semen sample at 1 and ≥3 months post-randomisation. The couple will be followed up for 12 weeks post-supplement cessation to report the outcome of any pregnancy.

Mechanistic testing will include number of semen, antioxidant balance and ROS, sperm chromatin & DNA structure and other relevant assays. Dietary information will also be taken.

Intervention type

Drug

Phase

Phase III

Drug names

MENEVIT dietary supplement

Primary outcome measure

Feasibility outcomes:
1. Proportion of screened men that are eligible for the trial on the basis of their baseline sperm sample
2. Proportion of eligible couples randomised
3. Proportion of potentially eligible men who consent to baseline sperm sample provision
4. Proportion of randomised men that return for their 1 month and 3 month follow-up visits for additional sperm sample provision
5. Men’s compliance to taking the daily nutritional supplement and reasons for stopping taking the trial intervention early
6. Proportion of couples that withdraw from the trial, and the reasons for this
7. Proportion of couple that are lost to follow-up

Secondary outcome measures

1. Mechanistic monitoring
1.1 Amount of sperm DNA damage relative to baseline after 1 month on the trial intervention
1.2 Changes in conventional sperm parameters after 1 month on the trial intervention
1.3 Amount of sperm DNA damage relative to baseline after 3 months on the trial intervention
1.4 Changes in conventional sperm parameters after 3 months on the trial intervention

2. Clinical monitoring
2.1 Ongoing pregnancy at 12 completed weeks of gestation
2.2 Spontaneous conception rates whilst the man is taking the treatment
2.3 Adverse events related to the trial intervention

3. Acceptability and impact on patients (outcome). All men will be requested to complete a short questionnaire at their 3-month follow-up visit to assess:
3.1 How the trial impacted on their day-to-day life, including the attendance of follow-up visits.
3.2 The acceptability of taking the daily nutritional supplement.
3.3 Suggestions for making improvements to the recruitment processes.

Overall trial start date

01/01/2019

Overall trial end date

25/12/2021

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

Male participants:
1. Aged 18 or over
2. Two or more previous unexplained miscarriages with their current female partner
3. Currently trying to conceive with their current female partner
4. Willing to provide repeated ejaculated sperm samples for analysis
5. Sperm DNA damage greater than or equal to 20% at baseline (as determined using the Birmingham TUNEL assay)

Female participants:
1. Aged 18 to 40
2. Willing to take folic acid supplement as per medical guidelines, this is not part of the trial and would be expected in routine practice for all patients

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 30; UK Sample Size: 30

Participant exclusion criteria

Male participants:
1. Previous participation in pAToMiUM
2. Current smoker
3. Unwilling to provide repeated ejaculated sperm samples for analysis
4. Evidence for bacterial infection in semen on baseline semen analysis
5. Currently taking dietary supplementation and unwilling to switch to the trial supplement alone
6. Known genetic cause of previous miscarriage (e.g. chromosomal translocation)

Female participants:
1. Participation in any other trial of an investigational medicinal product
2. Female partner is known to be pregnant at the time of randomisation
3. Known genetic cause of previous miscarriage (e.g. chromosomal translocation)

Recruitment start date

01/12/2019

Recruitment end date

01/07/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Tommy's National Miscarriage Centre, Birmingham Women's Hospital
Birmingham Women's & Children's NHS Foundation Trust Mindelsohn Drive Edgbaston
Birmingham
B15 2TG
United Kingdom

Sponsor information

Organisation

University of Birmingham

Sponsor details

Research Governance
The Finance Office
Aston Webb
The University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
+44 121 414 3698
researchgovernance@contacts.bham.ac.uk

Sponsor type

University/education

Website

http://www.birmingham.ac.uk/researchsupportgroup

Funders

Funder type

Government

Funder name

NIHR Academy; Grant Codes: Health Care Science SCL-2014-05-001

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Bayer HealthCare

Alternative name(s)

BHC

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

Germany

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal

IPD sharing statement:
The datasets generated during the current study will be available upon request from the Birmingham Clinical Trials Unit at the University of Birmingham in an anonymised format after the trial has been published. Requests for the sharing of data will be reviewed by a Data Sharing Committee

Intention to publish date

25/12/2022

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

22/07/2019: Trial’s existence confirmed by NIHR.