CaREFREE Study (Calorie Restriction, Environment and Fitness: Reproductive Effects Evaluation Study)
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|ClinicalTrials.gov Identifier: NCT02858336|
Recruitment Status : Recruiting
First Posted : August 8, 2016
Last Update Posted : September 5, 2018
Functional hypothalamic amenorrhea (functional HA) is a condition where a woman s period stops for a temporary time. This is due to improper function of the hypothalamus. This is the part of the brain that directs the whole reproductive system. Researchers want to learn more about functional HA. They also want to learn how diet, exercise, and other factors may change women s menstrual cycles.
To better understand functional HA.
Healthy women ages 18-28 years old who:
- Have regular periods
- Exercise no more than 4 hours a week
- Had their first period at age 11-14
Participants will be prescreened over the phone.
Participants will be screened with:
- Blood and urine tests
- Medical history
- Physical exam.
Participants will have 9 or 10 visits over about 3 menstrual cycles. These include:
- Repeat of screening tests
- Exercise test
- Resting energy expenditure test: Participants fast overnight before the test. They lie on their back under a
canopy for a half hour.
- Body composition test: This is done with a dual energy x-ray absorptiometry (DXA) scan.
- Pelvic ultrasound
- For two full-day visits, an IV is inserted into an arm vein. The IV takes a blood sample every 10 minutes for 8 hours.
Participants will keep logs:
- Menstrual cycle log
- Diet log for three 4-day cycles
Participants will receive test kits to complete at home:
- Daily blood and urine sample
Participants will take a daily iron supplement. They will wear a wristband that monitors activity 24 hours a day.
Participants will stick to a special diet for two 5-day periods of time. They will complete two 4-day exercise programs.
|Condition or disease||Intervention/treatment||Phase|
|Normal Physiology Healthy||Behavioral: NEA Behavioral: DEA||Early Phase 1|
Functional hypothalamic amenorrhea (HA) is a reversible form of hypogonadotropic hypogonadism (HH) that can be triggered by stressors such as exercise, nutritional deficits, and psychological stress. Dysfunction of the hypothalamic component of the reproductive axis plays a key role in functional HA and is manifest by an altered pattern of luteinizing hormone (LH) pulses detectable in peripheral blood. There is ample evidence supporting the use of LH as a surrogate marker of hypothalamic gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus. There is also significant evidence that women vary in their susceptibility to such stress-induced amenorrhea, pointing to a role for both environmental and genetic factors in the etiology of functional HA. However, the variation in changes in GnRH pulse frequency in response to stressors in healthy women has not been defined. Data from previous work in our lab has suggested that rare variants in genes associated with other forms of HH may also contribute to the variability seen in susceptibility to functional HA. The long-term goal of our research is to examine the interaction of environment and genes in HA. In this pilot study we propose to examine the inter-individual variability in pulsatile LH secretion in response to standardized neutral and deficient energy availability (NEA and DEA, respectively) in normal women. We will then relate this primary end-point to proposed predictive factors including past reproductive and family history and markers of current metabolic status and their response to energy availability. Our initial analyses will help to determine simplified biomarkers that can be translated to larger studies examining the potential combined effect of energy availability and genotype.
The proposed pilot study is a single-site, 2-period study in healthy female volunteers. The study will enroll approximately 150 participants over 2 years with a target for study completion of 25 subjects. Eligible participants will be females greater than or equal to 18 years of age. Eligible participants will have had menarche at or before 14 years of age and no earlier than age 11. Eligible participants will have a gynecological age (years after menarche) of 14 years or less. The upper age limit will vary based on each subject s age of menarche and fall between 25 and 28 among participants. Eligible participants will confirm at the pre-screening call having normal menstrual cycles (self-reported) for at least the previous 2 months and ovulation will be confirmed during the menstrual cycle before the start of intervention.
The primary outcome will be changes in daytime LH pulse frequency, when comparing NEA vs DEA. Secondary measures will evaluate past reproductive history, family history, and current metabolic status using medical history interviews, lifestyle questionnaires and maximum oxygen uptake (as a measure of fitness). Resting energy expenditure, body composition as well as metabolic and stress hormones will be measured at baseline and in association with the interventions. Blood samples will be collected for eventual genotyping.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||150 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||None (Open Label)|
|Official Title:||CaREFREE Study (Calorie Restriction, Environment and Fitness: Reproductive Effects Evaluation Study)|
|Study Start Date :||August 5, 2016|
|Estimated Primary Completion Date :||July 1, 2021|
|Estimated Study Completion Date :||July 1, 2021|
Active Comparator: Control
All participants will receive the NEA availability to act as their own control to the experimental DEA intervention.
Neutral Energy Availability: 5-day outpatient intervention of prescribed diet and exercise to elicit an energy availability of 45 kcal/kg LBM day.
All participants will be in the experimental arm and received the DEA intervention.
Deficient Energy Availability: 5-day outpatient intervention of prescribed diet and exercise to elicit an energy availability of 20 kcal/kg LBM day.
- The primary outcome measure will be change in daytime LH pulse frequency following 5 days of neutral energy availability as compared to LH pulse frequency following 5 days deficient energy availability. LH pulse frequency will be derived from 2 ... [ Time Frame: 10mins x 8hrs, 2days ]
- Change in hormone measures (LH, FSH, estradiol, and progesterone from daily urine samples and blood spots, total cycle, follicular and luteal phase length during the cycle following NEA or DEA [ Time Frame: 10mins x 8hrs, 2days ]
- Change in leptin, ghrelin, adiponectin, insulin, and glucose in response to standardized breakfast, lunch, and snack [ Time Frame: 10mins x 8hrs, 2days ]
- Change in cortisol, TSH, TT3, and fT4 [ Time Frame: 10mins x 8hrs, 2days ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02858336
|Contact: Lisa B Barber, MEd||(984) firstname.lastname@example.org|
|United States, North Carolina|
|NIEHS Clinical Research Unit (CRU)||Recruiting|
|Research Triangle Park, North Carolina, United States|
|Contact: Lisa Barber, M.Ed. 919-541-9847 email@example.com|
|Principal Investigator:||Janet E Hall, M.D.||National Institute of Environmental Health Sciences (NIEHS)|