Hot FlushesPhase 1FLASHNCT01141972
The Role of Vitamin D in Menopause: Relationship to Menopausal Symptoms in Body Composition
A Phase 1 study testing Vitamin D in people with Hot Flushes and Menopause, Premature, run by Kaiser Permanente at 1 site in United States.
Trial summary
Specific Aim 1: To compare effects of Vitamin D supplementation to usual care on symptoms in women transitioning to early postmenopause and determine the associated effect size in order to conduct a power analysis for a future RCT. Read more about this study
- Who is it for?
- Ages 40 to 60 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Hot Flushes, Menopause, Premature, Obesity
- What is being tested?
- Vitamin D
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2010to Feb 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 60 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Women in late menopausal transition or early menopause
- Age 40-55
- BMI >25 kg/m2
- Suffer from menopausal symptoms
- Change in previously regular cycles consisting of at least ≥2 skipped cycles and an interval of amenorrhea (≥60 days) in the last year
- Negative pregnancy test
- Vitamin D insufficiency (<30 ng/ml)
- Weight stability (+/- 5%) for 3 months
Who cannot join
- No period for >12 months
- Hormone use (i.e. menopausal hormone therapy, oral contraceptive, other hormonal medications) in last 3 months
- History of hysterectomy more than 11 months ago
- Abnormal screening blood tests (i.e. elevated serum calcium level, elevated creatinine)
- History of medical conditions where Vitamin D supplementation is not indicated (i.e. chronic renal insufficiency, elevated calcium, sarcoidosis or other granulomatous disease, lymphoma, or tuberculosis
- History of osteoporosis or osteoporosis on baseline DXA (expect less than 4% of screened population)84
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- Vitamin D deficiency (<10 ng/ml) as we felt it was unethical to withhold supplementation for 12 months in severe deficiency (according to our KPNW survey, this will exclude <2% of population)
- Consuming more than 400 IU of Vitamin D supplementation daily (we felt such doses taken outside of the study design could confound results)
- Current smoker (within the last year)
- Taking medications that affect body weight
- Prior bariatric surgery
- Taking medications or herbal supplements that affect mood (i.e. antidepressants) or menopausal symptoms (i.e. herbal meds) or sleep
- Weighing more than 400 pounds (cannot fit on DEXA scan)
- Not fluent in English or cognitively impaired
Trial locations and contacts
1 site in 1 country.
United States1 site
Kaiser Permanente Center for Health Research
Portland, Oregon, 97227
About this study
Specific Aim 1: To compare effects of Vitamin D supplementation to usual care on symptoms in women transitioning to early postmenopause and determine the associated effect size in order to conduct a power analysis for a future RCT. Hypothesis: Vitamin D insufficient women in early postmenopause who are randomized to supplementation, titrated to achieve sufficiency for 2 months, will have fewer symptoms including hot flashes, mood, and musculoskeletal complaints than women randomized to usual care.
Specific Aim 2: To compare effects of Vitamin D supplementation to usual care on body composition (by dual-energy x-ray absorptiometry [DXA] and by weight, BMI, waist to hip ratio) in overweight/obese women transitioning to early postmenopause and determine the associated effect size for a power analysis for a future RCT. Hypothesis: Vitamin D insufficient women in the menopausal transition randomized to supplementation, titrated to achieve sufficiency for 9 months, will improve DXA body composition (less total body and abdominal fat), compared to women in usual care, who will have increased body weight, including total and abdominal fat.
Specific Aim 3: To estimate the proportion of overweight/obese middle-aged women who achieve sufficiency by 1 month versus 2 or more months and to determine if achieving sufficiency by 1 month varies by baseline characteristics. Hypothesis: About 80% of participants will achieve sufficient Vitamin D level by 1 month. Those who need more than 1 month for sufficiency will have lower baseline levels and higher initial BMI.
Read the detailed description
It is increasingly recognized that Vitamin D deficiency affects more than just bone health. Links between Vitamin D deficiency have been established or purported for diabetes, the metabolic syndrome, cardiovascular disease, and cancer. We propose to explore if Vitamin D replacement (safe, readily available, and inexpensive) has beneficial effects on 2 novel outcomes in early postmenopausal women: menopause-related symptoms and body composition.
Most women transitioning through menopause, especially those with higher percent body fat, will experience hot flashes through a mean of 4 to 5 years. Many also have mood disturbances and muscle aches although the link with the menopausal transition is less clear. In many, these symptoms are severe enough to negatively impact their quality of life, work performance, and interpersonal relationships. Current treatments for menopause-related symptoms, such as menopausal hormone therapy, antidepressants, and anticonvulsants, have significant side effects and serious long term adverse consequences and symptoms recur after treatment discontinuation. A safe, inexpensive, well-tolerated treatment is therefore of high priority.
Both our preliminary data in early postmenopausal women and a 2010 publication of women on aromatase inhibitors for breast cancer show an association between Vitamin D deficiency and menopause-related symptoms including hot flashes. It is postulated that a contributor to hot flashes is a menopausal decline in serotonin, a neurotransmitter with known effects on thermoregulation. As Vitamin D can protect against experimental serotonin depletion in rats, one proposed mechanism for symptom alleviation is prevention of serotonin decline in menopause.
Both Vitamin D deficiency and the menopausal transition are associated with mood disturbances and musculoskeletal aches. Because estrogen increases the activity of the enzyme responsible for activating Vitamin D, the fall in estrogen that occurs during the menopausal transition could uncover previously subclinical Vitamin D deficiency. Indeed, Vitamin D can improved mood and muscle aches in non-menopausal populations, but its effects in menopausal women, where the benefits may be magnified, have not been previously studied.
- Conditions
- Hot Flushes, Menopause, Premature, Obesity, Vitamin D Deficiency
- Being tested
- Vitamin D, Placebo
- Keywords
- Vitamin D, Obesity, Menopause, Hot Flashes
- Medical subject headings
- Hot Flashes, Menopause, Premature, Obesity, Vitamin D Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin DDietary supplement
We will administer 100,000 IU Vitamin D3 orally as an observed 1-time bolus and then prescribe 1000 IU by mouth daily. These doses have achieved sufficiency in other populations.99, 100 We will use the level of sufficiency (≥30 ng/ml [≥75 nmol/L]) that is recommended by most experts in the field.89-91, 93, 95, 96, 101-105 We will repeat the bolus at 1 month if the target level is not achieved. The control group will receive matching placebo and a similar proportion will go through a dummy titration. All women consuming less than 800 mg/day of calcium (by dietary history) will receive 500 mg of calcium to ensure sufficiency.
PlaceboOther
Current standard of practice does not dictate that otherwise healthy early menopausal women have Vitamin D levels evaluated. Women with Vitamin D levels between 10 and 29 ng/ml who receive placebo will be receiving usual care (i.e., no additional Vitamin D repletion above intake at the time of screening).
| Study group | Role | What they receive |
|---|---|---|
| Supplement | Active comparator | We will administer 100,000 IU Vitamin D3 orally as an observed 1-time bolus and then prescribe 1000 IU by mouth daily. These doses have achieved sufficiency in other populations.99, 100 We will use the level of sufficiency (≥30 ng/ml [≥75 nmol/L]) that is recommended by most experts in the field.89-91, 93, 95, 96, 101-105 We will repeat the bolus at 1 month if the target level is not achieved. The control group will receive matching placebo and a similar proportion will go through a dummy titration. All women consuming less than 800 mg/day of calcium (by dietary history) will receive 500 mg of calcium to ensure sufficiency Receives: Dietary Supplement: Vitamin D |
| Placebo | Placebo comparator | Current standard of practice does not dictate that otherwise healthy early menopausal women have Vitamin D levels evaluated. Women with Vitamin D levels between 10 and 29 ng/ml who receive placebo will be receiving usual care (i.e., no additional Vitamin D repletion above intake at the time of screening). Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
compare effects of Vitamin D supplementation to usual care on symptoms in women transitioning to early postmenopause and determine the associated effects
Vitamin D levels will be measured at baseline, after dose adjustments, and at the 3 month and final visit.
Measured: 12 months
Secondary outcomes (1)
compare effects of Vitamin D supplementation to usual care on body composition (by dual-energy x-ray absorptiometry [DXA] and by weight, BMI, waist to hip ratio) in overweight/obese women transitioning to early postmenopause
Body composition will be measured with DXA113, 114 and anthropometric techniques (weight, height, BMI, waist to hip ratio)
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2010 (estimated)
- Study startSep 2010
- Primary completionFeb 2012
- Study completionFeb 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hot FlushesStudies of the same condition, open and under way.
- More trials run by Kaiser PermanenteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kaiser Permanente
- Sponsor type
- University, hospital or other
- Collaborators
- Oregon Health and Science University
- Responsible party
- Sponsor
- Investigators
- Erin S. LeBlanc, MD, MPH, Principal investigator, Kaiser Permanente
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01141972
- Sponsor's protocol ID
- Pro00001445
- Acronym
- FLASH
- Status last verified
- May 2012
- First submitted
- 9 Jun 2010
- Last updated
- 30 May 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Vitamin D in Menopause: Relationship to Menopausal Symptoms in Body Composition
- ClinicalTrials.gov ID
- NCT01141972
- Acronym / sponsor ID
- FLASH / Pro00001445
- Conditions
- Hot Flushes, Menopause, Premature, Obesity, Vitamin D Deficiency
- Keywords
- Vitamin D, Obesity, Menopause, Hot Flashes
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Kaiser PermanenteUniversity, hospital or other
- Collaborators
- Oregon Health and Science University
- Study start
- Sep 2010
- Primary completion
- Feb 2012 (actual)
- Study completion
- Feb 2012 (actual)
- First posted
- 11 Jun 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Specific Aim 1: To compare effects of Vitamin D supplementation to usual care on symptoms in women transitioning to early postmenopause and determine the associated effect size in order to conduct a power analysis for a future RCT. Hypothesis: Vitamin D insufficient women in early postmenopause who are randomized to supplementation, titrated to achieve sufficiency for 2 months, will have fewer symptoms including hot flashes, mood, and musculoskeletal complaints than women randomized to usual care.
Specific Aim 2: To compare effects of Vitamin D supplementation to usual care on body composition (by dual-energy x-ray absorptiometry [DXA] and by weight, BMI, waist to hip ratio) in overweight/obese women transitioning to early postmenopause and determine the associated effect size for a power analysis for a future RCT. Hypothesis: Vitamin D insufficient women in the menopausal transition randomized to supplementation, titrated to achieve sufficiency for 9 months, will improve DXA body composition (less total body and abdominal fat), compared to women in usual care, who will have increased body weight, including total and abdominal fat.
Specific Aim 3: To estimate the proportion of overweight/obese middle-aged women who achieve sufficiency by 1 month versus 2 or more months and to determine if achieving sufficiency by 1 month varies by baseline characteristics. Hypothesis: About 80% of participants will achieve sufficient Vitamin D level by 1 month. Those who need more than 1 month for sufficiency will have lower baseline levels and higher initial BMI.
Detailed description
It is increasingly recognized that Vitamin D deficiency affects more than just bone health. Links between Vitamin D deficiency have been established or purported for diabetes, the metabolic syndrome, cardiovascular disease, and cancer. We propose to explore if Vitamin D replacement (safe, readily available, and inexpensive) has beneficial effects on 2 novel outcomes in early postmenopausal women: menopause-related symptoms and body composition.
Most women transitioning through menopause, especially those with higher percent body fat, will experience hot flashes through a mean of 4 to 5 years. Many also have mood disturbances and muscle aches although the link with the menopausal transition is less clear. In many, these symptoms are severe enough to negatively impact their quality of life, work performance, and interpersonal relationships. Current treatments for menopause-related symptoms, such as menopausal hormone therapy, antidepressants, and anticonvulsants, have significant side effects and serious long term adverse consequences and symptoms recur after treatment discontinuation. A safe, inexpensive, well-tolerated treatment is therefore of high priority.
Both our preliminary data in early postmenopausal women and a 2010 publication of women on aromatase inhibitors for breast cancer show an association between Vitamin D deficiency and menopause-related symptoms including hot flashes. It is postulated that a contributor to hot flashes is a menopausal decline in serotonin, a neurotransmitter with known effects on thermoregulation. As Vitamin D can protect against experimental serotonin depletion in rats, one proposed mechanism for symptom alleviation is prevention of serotonin decline in menopause.
Both Vitamin D deficiency and the menopausal transition are associated with mood disturbances and musculoskeletal aches. Because estrogen increases the activity of the enzyme responsible for activating Vitamin D, the fall in estrogen that occurs during the menopausal transition could uncover previously subclinical Vitamin D deficiency. Indeed, Vitamin D can improved mood and muscle aches in non-menopausal populations, but its effects in menopausal women, where the benefits may be magnified, have not been previously studied.
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Supplement | Active comparator | Dietary Supplement: Vitamin DWe will administer 100,000 IU Vitamin D3 orally as an observed 1-time bolus and then prescribe 1000 IU by mouth daily. These doses have achieved sufficiency in other populations.99, 100 We will use the level of sufficiency (≥30 ng/ml [≥75 nmol/L]) that is recommended by most experts in the field.89-91, 93, 95, 96, 101-105 We will repeat the bolus at 1 month if the target level is not achieved. The control group will receive matching placebo and a similar proportion will go through a dummy titration. All women consuming less than 800 mg/day of calcium (by dietary history) will receive 500 mg of calcium to ensure sufficiency |
| Placebo | Placebo comparator | Other: PlaceboCurrent standard of practice does not dictate that otherwise healthy early menopausal women have Vitamin D levels evaluated. Women with Vitamin D levels between 10 and 29 ng/ml who receive placebo will be receiving usual care (i.e., no additional Vitamin D repletion above intake at the time of screening). |
Who may qualify
- Ages
- 40 to 60 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Women in late menopausal transition or early menopause
- Age 40-55
- BMI >25 kg/m2
- Suffer from menopausal symptoms
- Change in previously regular cycles consisting of at least ≥2 skipped cycles and an interval of amenorrhea (≥60 days) in the last year
Key exclusion criteria (14 listed)
- No period for >12 months
- Hormone use (i.e. menopausal hormone therapy, oral contraceptive, other hormonal medications) in last 3 months
- History of hysterectomy more than 11 months ago
- Abnormal screening blood tests (i.e. elevated serum calcium level, elevated creatinine)
- History of medical conditions where Vitamin D supplementation is not indicated (i.e. chronic renal insufficiency, elevated calcium, sarcoidosis or other granulomatous disease, lymphoma, or tuberculosis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vitamin DWe will administer 100,000 IU Vitamin D3 orally as an observed 1-time bolus and then prescribe 1000 IU by mouth daily. These doses have achieved sufficiency in other populations.99, 100 We will use the level of sufficiency (≥30 ng/ml [≥75 nmol/L]) that is recommended by most experts in the field.89-91, 93, 95, 96, 101-105 We will repeat the bolus at 1 month if the target level is not achieved. The control group will receive matching placebo and a similar proportion will go through a dummy titration. All women consuming less than 800 mg/day of calcium (by dietary history) will receive 500 mg of calcium to ensure sufficiency. | Dietary supplement | Supplement |
| PlaceboCurrent standard of practice does not dictate that otherwise healthy early menopausal women have Vitamin D levels evaluated. Women with Vitamin D levels between 10 and 29 ng/ml who receive placebo will be receiving usual care (i.e., no additional Vitamin D repletion above intake at the time of screening). | Other | Placebo |
Primary outcome
compare effects of Vitamin D supplementation to usual care on symptoms in women transitioning to early postmenopause and determine the associated effects
Time frame: 12 months
Vitamin D levels will be measured at baseline, after dose adjustments, and at the 3 month and final visit.
1 secondary outcome
compare effects of Vitamin D supplementation to usual care on body composition (by dual-energy x-ray absorptiometry [DXA] and by weight, BMI, waist to hip ratio) in overweight/obese women transitioning to early postmenopause
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Erin S. LeBlanc, MD, MPH principal investigator
Kaiser Permanente
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Vitamin D in people with Hot Flushes and Menopause, Premature, run by Kaiser Permanente at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 May 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
compare effects of Vitamin D supplementation to usual care on symptoms in women transitioning to early postmenopause and determine the associated effects (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 May 2013.