Effect of chemotherapy and ionising radiation on sperm nuclear and mitochondrial DNA: Can pre-treatment with GnRH Agonists reverse these effects?
| ISRCTN | ISRCTN77877146 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN77877146 |
| Secondary identifying numbers | N0265055944 |
- Submission date
- 30/09/2005
- Registration date
- 30/09/2005
- Last edited
- 13/03/2014
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Urological and Genital Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English Summary
Not provided at time of registration
Contact information
Dr P Mahendra
Scientific
Scientific
Clinical Haematology
Queen Elizabeth Hospital
Birmingham
B15 2TH
United Kingdom
Study information
| Study design | Randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Not Specified |
| Scientific title | |
| Study hypothesis | 1. To examine whether chemotherapy/radiotherapy induced azoospermia/severe oligozoospermia can be reduced or prevented by 'down-regulation' of the pituitary using GnRH agonists. 2. If partial or complete gonadal protection is conferred by GnRH, will the sperm subsequently produced be damaged genetically? 3. If previously impaired sperm production in (due to the nature of the malignancy) improve post protective treatment with GnRHA? 4. To examine the effects of chemotherapeutic agents on sperm nuclear and mitochondrial DNA and the induction of apoptosis. |
| Ethics approval(s) | Not provided at time of registration |
| Condition | Urological and Genital Diseases |
| Intervention | The investigations will comprise the following: Sperm Storage Immediately on referral, patients will be given the opportunity to have spermatozoa cryopreserved at the ACU, Birmingham Women's Hospital. Briefly, after a full semen analysis (see below) and completion of relevant documentation, an equal amount of cryoprotectant media is added to the semen over a period of 10-15 minutes. Vials are then suspended in liquid nitrogen vapour. Semen Analysis Full semen analysis, including sperm concentration; motility; morphology; antisperm antibodies. vitality are carried out in accordance with the World Health organisation (WHO, 1992). Computer assisted sperm motility analysis (CASA) will also be performed, using an Hamilton Thorn IVOS (version 8.1).(Tomlinson Ct al, 1993). Blood tests Bloods for serum FSH and testosterone will be taken at the time of semen analyses. Sperm nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) Sperm nuclear DNA Damage will be assessed using the TUNEL assay or using the sperm nuclear cliromatin integrity analysed using the Chromomycin A3 fluorochrome (Manicardi et al, 1995; 1998) Mitochondrial DNA fragmentation will be studied using long PCR according to the methods of St.John, (in press). Mitochondrial Function Mitochondrial membrane potential will be assessed using the fluorescent probe D1Oc6 counterstained with propidium iodide for sperm viability according to the methods Zamzami et al (1996). Samples Samples will be assessed immediately after referral from the oncology centres. A second sample will be assessed 3 months later and then again at 6 months. All the above mentioned techniques have been developed and validated and are in current use in our laboratories. |
| Intervention type | Other |
| Primary outcome measure | Not provided at time of registration |
| Secondary outcome measures | Not provided at time of registration |
| Overall study start date | 01/10/2003 |
| Overall study end date | 01/01/2007 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Male |
| Target number of participants | Not provided at time of registration |
| Participant inclusion criteria | Patients will be referred from tertiary referral centres in Birmingham. These will include principally the Queen Elizabeth Hospital in Edgbaston, Selly Oak Hospital and the Dept of Haematology, Heartlands Hospital. They will have been referred for sperm storage to prior to chemo or radiotherapy mainly in cases of malignant disease but also in other conditions e.g. treatment of nephrotic syndrome. Patients will be randomised to treatment groups at the point of intention to treat. |
| Participant exclusion criteria | Not provided at time of registration |
| Recruitment start date | 01/10/2003 |
| Recruitment end date | 01/01/2007 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Clinical Haematology
Birmingham
B15 2TH
United Kingdom
B15 2TH
United Kingdom
Sponsor information
Department of Health
Government
Government
Richmond House
79 Whitehall
London
SW1A 2NL
United Kingdom
| Phone | +44 (0)20 7307 2622 |
|---|---|
| dhmail@doh.gsi.org.uk | |
| Website | http://www.dh.gov.uk/Home/fs/en |
Funders
Funder type
Government
University Hospital Birmingham NHS Trust (UK)
No information available
Research Funds
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
