Pilot antioxidant therapy of men in unexplained miscarriage: the pAToMiUM trial
| ISRCTN | ISRCTN91556363 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN91556363 |
| EudraCT/CTIS number | 2019-000315-91 |
| Secondary identifying numbers | 42663 |
- Submission date
- 15/07/2019
- Registration date
- 05/09/2019
- Last edited
- 19/08/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Pregnancy and Childbirth
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
Contact information
Scientific
Centre for Human Reproductive Science
Institute for Biomedical Research
Vincent Drive, Edgbaston
The University of Birmingham
Birmingham
B15 2TG
United Kingdom
 ORCID ID |
0000-0003-2833-8970 |
|---|---|
| Phone | +44 121 414 5867 |
| j.kirkmanbrown@bham.ac.uk |
Study information
| 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 |
| Study setting(s) | Hospital |
| Study type | Prevention |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | The pAToMiUM trial - pilot Antioxidant Therapy of Men in Unexplained Miscarriage |
| Study 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(s) | 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 |
| 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | 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 study start date | 01/01/2019 |
| Overall study end date | 28/07/2023 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 30; UK Sample Size: 30 |
| Total final enrolment | 15 |
| 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 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 | 03/08/2022 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Mindelsohn Drive
Edgbaston
Birmingham
B15 2TG
United Kingdom
Sponsor information
University/education
Research Governance
The Finance Office
Aston Webb
The University of Birmingham
Edgbaston
Birmingham
B15 2TT
England
United Kingdom
| Phone | +44 121 414 3698 |
|---|---|
| researchgovernance@contacts.bham.ac.uk | |
| Website | http://www.birmingham.ac.uk/researchsupportgroup |
"ROR" |
https://ror.org/03angcq70 |
Funders
Funder type
Government
No information available
Private sector organisation / For-profit companies (industry)
- Alternative name(s)
- BHC
- Location
- Germany
Results and Publications
| Intention to publish date | 31/10/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | 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 |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
19/08/2022: The following changes have been made:
1. The recruitment end date has been changed from 01/07/2020 to 03/08/2022.
2. The overall trial end date has been changed from 25/12/2021 to 28/07/2023 and the plain English summary updated accordingly.
3. The intention to publish date has been changed from 25/12/2022 to 31/10/2023.
4. Recruitment had resumed.
5. The final enrolment number has been added
15/04/2020: Due to current public health guidance, recruitment for this study has been paused.
22/07/2019: Trial’s existence confirmed by NIHR.
