Condition category
Cancer
Date applied
11/03/2015
Date assigned
11/03/2015
Last edited
25/08/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Scientific

Primary contact

Ms Claire Gaunt

ORCID ID

Contact details

School of Cancer Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom

Additional identifiers

EudraCT number

2013-004246-41

ClinicalTrials.gov number

Protocol/serial number

18588

Study information

Scientific title

A phase III randomised study of folic acid supplementation in the management of menopausal symptoms in cancer survivors and healthy postmenopausal women

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

14/WM/0093; First MREC approval date 06/05/2014

Study design

Randomised; Interventional; Design type: Screening, Treatment

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Treatment

Patient information sheet

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

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

Phase

Drug names

Primary outcome measures

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 trial start date

08/02/2015

Overall trial end date

31/10/2017

Reason abandoned

Eligibility

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 type

Patient

Age group

Adult

Gender

Female

Target number of participants

Planned Sample Size: 236; UK Sample Size: 236

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

31/07/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University of Birmingham
School of Cancer Sciences Edgbaston
Birmingham
B15 2TT
United Kingdom

Sponsor information

Organisation

University of Birmingham

Sponsor details

Edgbaston
Birmingham
B15 2TT
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

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)