Folic acid supplementation in the management of menopausal symptoms in cancer survivors and healthy postmenopausal women
| ISRCTN | ISRCTN98158824 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN98158824 |
| EudraCT/CTIS number | 2013-004246-41 |
| Secondary identifying numbers | 18588 |
- Submission date
- 11/03/2015
- Registration date
- 11/03/2015
- Last edited
- 10/11/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English Summary
Contact information
Ms Claire Gaunt
Scientific
Scientific
School of Cancer Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
Study information
| Study design | Randomised; Interventional; Design type: Screening, Treatment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Other |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a patient information sheet |
| Scientific title | A phase III randomised study of folic acid supplementation in the management of menopausal symptoms in cancer survivors and healthy postmenopausal women |
| Study acronym | FOAM |
| Study hypothesis | FOAM is a phase III, double-blind, placebo-controlled, randomised controlled trial designed to determine whether folic acid supplementation improves the frequency and severity of hot flushes in postmenopausal women, either healthy women or breast and endometrial cancer survivors compared to placebo. The frequency and severity of hot flushes will be recorded on self reporting patient diaries. Effectiveness of folic acid supplementation on other menopausal symptoms, and quality of life will also be investigated. If folic acid is demonstrated to be effective, it would represent a cheap, safe, well tolerated and easily deliverable alternative to the conventional hormone replacement therapy, particularly in cancer survivors who may be experiencing more intense symptoms and certainly cannot take hormone replacement. |
| Ethics approval(s) | 14/WM/0093; First MREC approval date 06/05/2014 |
| Condition | Topic: Cancer; Subtopic: Breast Cancer; Disease: Breast |
| Intervention | Folic Acid: Folic acid is a member of the B group of vitamins. It participates in cellular division, DNA synthesis and maturation of red blood cells. Patients randomised to the Folic Acid arm will take 5 mg/day; Follow Up Length: 0 month(s); Study Entry : Single Randomisation only |
| Intervention type | Supplement |
| Primary outcome measure | Change in Hot Flush Score; Timepoint(s): Change in Hot Flush Score at 12 weeks from randomisation. |
| Secondary outcome measures | 1. Change in 5-HIAA levels and MHPG metabolites; Timepoint(s): In urine from randomisation at week 12 2. Change in frequency of hot flushes; Timepoint(s): Change from randomisation in frequency of hot flushes (mild,moderate and severe) at weeks 4, 8 and 12 3. Change in longitudinal QoL data; Timepoint(s): As measured by the Utian Quality of Life Scale at weeks 4, 8 and 12 4. Change in other menopausal symptoms; Timepoint(s): Using the Greene Climacteric Scale at weeks 4, 8 and 12 5. Change in whole blood levels of serotonin, plasma nor-adrenaline and serum folic acid; Timepoint(s): From randomisation at week 12 6. Correlation of blood changes with clinical improvement; Timepoint(s): Changes in whole blood levels of serotonin, nor-adrenaline, and serum folic acid at week 12 7. Effects in specific prognostic subgroups; Timepoint(s): Healthy women vs cancer survivors and BMI <30 v >30 8. Interim Change in Hot Flush Score; Timepoint(s): Change from randomisation in Hot Flush Score at weeks 4, 8 and 12 9. Percentage of responders; Timepoint(s): The percentage of responders at weeks 4, 8 and 12; defined as a reduction in Hot Flush Score of =50% |
| Overall study start date | 08/02/2015 |
| Overall study end date | 31/10/2017 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Female |
| Target number of participants | Planned Sample Size: 236; UK Sample Size: 236 |
| Total final enrolment | 164 |
| Participant inclusion criteria | 1. Experiencing =50 hot flushes per week, as quantified from daily patient Sloan Diary recordings for 7 days after consent and prior to randomisation 2. Being =40 and =70 years of age 3. Willing to participate in the trial and given informed consent; Target Gender: Female |
| Participant exclusion criteria | As of 25/08/2016: 1. Baseline red cell serum folic acid level above the normal laboratory range (3.1 to 20.0µg/L) 2. Smoking >5 cigarettes per day 3. Intestinal malabsorption e.g. coeliac, tropical sprue or Crohn’s disease 4. Known chronic renal impairment or failure 5. Known established chronic conditions mimicking climacteric presentation e.g. poorly controlled hypertension, hyperglycaemia or thyroid instability 6. Pernicious anaemia due to vitamin B12 deficiency 7. Alcohol consumption more than 14 units per week 8. Women with phaeochromocytoma or other medullary tumours or carcinoid syndrome 9. Known allergic reactions and/or hypersensitivity to folic acid 10. Women who are, in the opinion of the treating physician, unlikely to be able to give informed consent or successfully complete the trial intervention and procedure 11.Participation in another clinical trial within the last 4 weeks prior to enrolment 12. Administration of the following drugs during study and for the specified number of weeks prior to study entry: 12.1. 24 weeks prior to randomisation: 12.1.1 Bevacizumab (Avastin) 12.1.2. Trastuzumab (Herceptin) 12.2. 8 weeks prior to randomisation: 12.2.1. HRT (women on oestrogen implants are excluded from trial entry) 12.2.2. Herbal remedies 12.2.3. Heparin 12.3. 6 weeks prior to randomisation: 12.3.1. Tamoxifen 12.3.2. Fluoxetine 12.3.3. Venlafaxine 12.4. 4 weeks prior to randomisation: 12.4.1. Phenytoin 12.4.2. Phenobarbitol 12.4.3. Primidone 12.5. 2 weeks prior to randomisation: 12.5.1. Warfarin 12.5.2. Sertraline 12.5.3. Mianserin 12.5.4. Mirtazapine 12.6. 1 week prior to randomisation: 12.6.1. Raloxifen 12.6.2. Chronic use of NSAIDs (including high dose Aspirin* and Cox-2 inhibitors) 12.6.3. Methotrexate 12.6.4. Fluorouracil 12.6.5. Trimethoprim 12.6.6. Co-trimoxazole 12.6.7. Chloramphenicol 12.6.8. Sulfasalazine 12.6.9. Paroxetine 12.6.10. Duloxetine 12.6.11. Clonidine *low dose Aspirin (75mg daily) is not prohibited 12.7. Stop prior to study entry: 12.8. Cholestyramine 12.9. Antacids (containing aluminium or magnesium) 12.10. Vitamin containing zinc or folic acid Initial 1. Hormonal or non hormonal treatment (including raloxifen) for menopausal symptoms within 8 weeks of enrolment 2. Baseline serum folic acid level which is above the normal laboratory range (3.1 to 20.0µg/L) 3. Smoking >5 cigarettes per day 4. Intestinal malabsorption e.g. celiac, tropical sprue or Crohn’s disease 5. Known chronic renal impairment or failure 6. Pernicious anaemia due to vitamin B12 deficiency 7. Taking the following drugs: 7.1. Nonsteroidal antiinflammatory drugs (NSAIDs) can interfere with folate metabolism 7.2. Cholestrollowering agents such as cholestryamine may decrease folic acid absorption 7.3. Chemotherapeutic agents such as fluorouracil and methotrexate can interfere with conversion of folate into tetrahydrofolate 7.4. Antibiotics such as chloramphenicol, trimethoprim and cotrimoxazole may inhibit dihydrofolic reductase 7.5. Sulfasalazine may decrease folic acid absorption 7.6. Anticonvulsants such as phenytoin, phenobarbital and primidone can interfere with absorption of anticonvulsants 7.7. Serotonin reuptake inhibitors such as fluoxetine, venlafaxine, sertraline and paroxetine may ameliorate hot flushes 7.8. Serotonin disinhibitants such as mianserin and mirtazapine may ameliorate hot flushes 7.9. a2adrenergic agonist such as yohimbine may aggravate hot flushes 7.10. a2adrenergic antagonist such as clonidine may ameliorate hot flushes 7.11. Antacids containing aluminium or magnesium can interfere with folate metabolism 7.12. Preparations containing zinc such as vitamins or food supplements that may contain folic acid 7.13. Anticoagulant or thrombolytic therapy can interfere with folate assays 8. Therapies containing human antimouse antibodies (e.g. Trastuzumab and Bevacizumab) can interfere with folate assays 9. Alcohol consumption more than 14 units per week 10. Women with phaeochromocytoma or other medullary tumours or carcinoid syndrome 11. Known allergic reactions and/or hypersensitivity to folic acid 12. Women who are, in the opinion of the treating physician, unlikely to be able to give informed consent or successfully complete the trial intervention and procedures 13. Participation in another clinical trial within the last 4 weeks prior to enrolment |
| Recruitment start date | 15/04/2015 |
| Recruitment end date | 30/04/2019 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
University of Birmingham
School of Cancer Sciences
Edgbaston
Birmingham
B15 2TT
United Kingdom
Edgbaston
Birmingham
B15 2TT
United Kingdom
Sponsor information
University of Birmingham
Hospital/treatment centre
Hospital/treatment centre
Edgbaston
Birmingham
B15 2TT
England
United Kingdom
"ROR" |
https://ror.org/03angcq70 |
|---|
Funders
Funder type
Government
National Institute for Health Research
Government organisation / National government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
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 | The current data sharing plans for this study are unknown and will be available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 01/11/2021 | 18/11/2021 | Yes | No | |
| Plain English results | 10/11/2022 | No | Yes | ||
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
10/11/2022: Cancer Research UK plain English results link added.
18/11/2021: Publication reference added.
30/05/2019: The following was updated:
1. The total final enrolment was added.
2. The recruitment end date was updated from 31/07/2017 to 30/04/2019.
25/08/2016: Changed study contact name. Changed recruitment start date from 18/02/2015 to 15/04/2015. Changed recruitment end date from 19/02/2017 to 31/07/2017. Changed overall study start date from 18/02/2015 to 08/02/2015. Changed overall study end date from 19/02/2017 to 31/10/2017. Changed participation inclusion criteria (date stamped in record)
