Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02190097 |
| Other study ID # |
14-13770 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
January 2015 |
| Est. completion date |
August 29, 2022 |
Study information
| Verified date |
November 2022 |
| Source |
University of California, San Francisco |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Polycystic ovary syndrome (PCOS) is a syndrome which includes elevated androgen levels,
irregular menstrual cycles and insulin resistance. Standard treatments, which include weight
loss and medications to improve insulin secretion are only partly successful, and may require
that young women take medications for decades.
The study investigators have been evaluating the effects of specific diets on insulin
resistance in healthy volunteers and subjects with type 2 diabetes, and have found that
subjects with insulin resistance seem to respond particularly well to these diet regimens.
Volunteers with PCOS are being asked to participate to see if following these diets can help
regularize your menstrual cycles. The results of this study may help improve fertility
treatments for women with PCOS.
Description:
Experimental Design and Methods This is a prospective, open labeled, randomized diet
intervention study done on adult participants with PCOS. After signing informed consents,
participants will be asked to eat a recommended ADA diet for two weeks (run in period).
Participants will then have baseline testing, including: urine and blood tests to evaluate
insulin resistance (fasting glucose and insulin, 2 hour oral glucose tolerance test),
electrolytes to assess acid-base status, ovarian volume and testosterone levels measured to
assess severity of PCOS, and questionnaires about menstrual frequency, eating habits and
stress. Participants will then be randomized to either a high fruits and vegetable Paleo Diet
for 4-8 months or a standard ADA-recommended diet for the first 4 months followed by Paleo
Diet for 0-4 months.All participants will have the option of limiting their participation to
just 4 months or extending participation to the full 8 months depending on their ongoing
level of interest. All testing will be repeated at 4 months (crossover point) and at
completion of the diets at 8 months. The primary outcome variables are menstrual cycle
frequency and ovarian volume, and secondary outcomes include metabolic profiles and
eating/behavior questionnaires
Procedures
1. Diet: All participants will initially be given diet information on ADA diet for the "Run
In" period , including printed ADA diet instructions and advice on caloric intake. The
ADA diet includes foods that are excluded in the Paleo Diet, such as grains, legumes and
dairy products and will also contain less potassium. All participants will be instructed
not to add salt to their food when cooking or eating. At 2 weeks, participants will be
randomized to Paleo Diet arm or ADA diet arm. Participants on the Paleo Diet arm will
require a "ramp-up" phase for one week (start out with 1 Paleo meal per day, then two,
and then all meals will be on a Paleolithic-type menu, which contains approximately an
average of 142 grams of protein and 12,200 mg of potassium per 3000 kcal. Participants
on the ADA diet arm will continue on the run-in diet.
After 16 weeks, the participants in the ADA arm will be changed over to the Paleo arm if
they wish to continue participation. They will also require a "ramp-up" phase for 1
week. In our previous studies, we have seen a crossover effect at one month going from
the Paleo to the ADA diet, but not from the ADA to the Paleo arm.
We will give all participants pertinent websites and written information about their
specific diet, as well as sample menus. We will give participants in the Paleo arm a
list of foods to avoid (e.g., dairy, grains, legumes, processed foods).
The main obstacles to compliance with outpatient diets include the cost, the amount of
time needed, and ignorance about where to get specific kinds of foods. We will give them
lists of various supermarkets and farmers markets times and dates, we will advise
participants about making up batches of foods on the weekends and freezing them, and if
they have families or other support, we will try to get them involved in support.
2. Monitoring dietary compliance: We will monitor compliance in a number of ways.
We have recruited four nutrition student volunteers from UC Berkeley, who will work closely
with the participants to help them adapt the study diets to their everyday living situations.
The nutrition students will help design the materials we will give the participants, as well
as give dietary advice. We are working on a number of electronic and social media methods for
keeping track of what our subjects are eating. These include:
- Initially daily, or near daily contacts for the first week of each diet, then at least
weekly contacts, and then at least monthly contacts.
- online data system that monitors food and activity (e.g., the USDA super tracker,
myfitnesspal, etc).
- tweets or texts that ask the subjects to go to an elink and answer a few questions,
e.g., did you eat grains today? The answers are downloaded to a database that can be
compiled to reflect dietary compliance for each subject.
We will also develop a secure website so that participants from each group can discuss with
others what problems and solutions they are using.
Last, we will also assess 24 hour urines for creatinine, sodium, and potassium at 0, 16 and
32 weeks. Both of these diets will be higher in potassium and lower in sodium than typical
American diets. Although we expect our subjects will be motivated enough to follow these
diets, from our previous studies we have found that some subjects were not honest about what
they were eating, and this was reflected in the 24 hour urine excretion of potassium and
sodium.
Assays:
Samples will be drawn at time 0; week 8; week 16; week 24 and week 32. We will collect serum,
plasma and urine at all these timepoints for banking. The following tests will be performed
at time (table 2):
1. CBC, Chemical profile; blood lipids; cardiovascular risk factors and inflammatory
cytokines and adipokines (time 0, week 16, week 32): Electrolytes, liver function tests,
fasting glucose, lipid panel and insulin levels will be measured by Quest labs. PAI-1
will be measured by a colorimetric assay (Chemicon, Temecula, CA). Homocysteine,
fibrinogen, hsCRP and ICAM-1 will be assayed by the UCSF clinical laboratory using
standard analytical methods. Commercial kits will be used to measure fasting serum
non-esterified fatty acids (Wako Diagnostics kit ;Richmond Virginia); serum TNF-α ,
IL-6, adiponectin and leptin (Quantikine HS high sensitivity ELISA ;R & D Systems,
Minneapolis, MN
2. Systemic oxidative stress (time 0, weeks 16, 32): we will measure 4 serum markers of
oxidative stress; protein carbonyls (a product of protein oxidation), TBARS (a
measurement of lipid peroxidation), TRAP (a measure of total antioxidant activity), and
isoprostanes (formed from the peroxidation of arachidonic acid in lipoproteins and
membranes). Blood samples will be drawn in the fasted state both at initial screening
and after ALA treatment. Protein carbonyls, TBARS, and TRAP will be performed at UC
Davis Clinical Laboratories employing standard techniques. Serum 8-isoprostane-F2α will
be measured by KRONOS Science laboratory, Phoenix Arizona. We will also measure urine
markers of oxidative stress before and after CRLA treatment. These will include
8-isoprostane-F2α, and 8-hydroxy guanosine (a marker of oxidized DNA). These urine
assays will be performed KRONOS Science laboratory, Phoenix Arizona and Dr Jack Roberts,
Vanderbilt University.
3. Telomere assessment. The length of telomeres, the DNA caps at the ends of chromosomes,
is emerging as an indicator of stress-related biological aging: Data have implicated
accelerated telomere shortening in the context of increased psychological stress and
stress arousal [10, 11]Blood drawn by a licensed phlebotomist (4 mL for telomere
assessment) at baseline (0 weeks) and 16-weeks will be assayed for telomere length.
Samples will be frozen and transferred on dry ice to the Blackburn Laboratory at UCSF,
located at 600 16th Street, San Francisco, California, by a laboratory technician.
Assays will be completed according to the polymerase chain reaction (PCR) method..
4. 24 hr urine collections . collections as per clinical protocol. We will measure volume,
Na, K, pH, creatinine and calcium
Reproductive testing:
Subjects will undergo assessment of 1)SHBG and androgen levels: total testosterone,
androstenedione and DHEAS; 2) clinical hyperandrogenism: hirsutism by modified
Ferriman-Gallwey and acne scores; 3) menstrual cyclicity (cycle interval and pattern);
and 4) ovarian morphology (follicle count and ovarian volume).
Androgen levels (times 0, weeks 16, 32): Two serum samples will be obtained 30 minutes
apart.. Serum will be isolated and aliquoted for future analysis of androstenedione (A),
testosterone (T), DHEAS, 17 hydroxyprogesterone (17-OHP) and SHBG.
Clinical hyperandrogenism: The presence and extent of hirsutism will be determined using
a modification of the Ferriman-Gallwey (FG) scoring method[12] while acne will be scored
according to the American Academy of Dermatology .Subjects will be requested to avoid
any mechanical treatment for hair removal for 4 weeks prior to the baseline visit and to
list all such treatments that are utilized during the study and their frequency.
Menstrual cyclicity: Menstrual frequency will be assessed as a menstrual frequency ratio
as described by Elkind-Hirsch [13]so that menstrual events are normalized to the normal
interval of 12 menses per year (MFR=1.0) or, for instance, those with 6 cycles per year
would have an MFR of 0.5.
Ovarian morphology: All subjects will undergo a transvaginal ultrasound (TVUS) to obtain
an antral follicle count at baseline, 8 and 16 weeks. The study investigator will image
both the left and right adnexal areas in two planes, and make measurements of the
transverse, longitudinal, and anteroposterior diameters of each ovary using electronic
calipers on a Shimadzu SDU-450XL machine with a variable 4-8 mHz vaginal transducer. The
examination of each adnexa will ensure an adequate opportunity to locate the organs.
Inability to locate adnexa in this age group is less than 1% (internal data). All
echo-free structures in the ovaries will be regarded as follicles. Follicles with a mean
diameter (of two dimensions) between 2 and 10 mm will be counted. Calculation of all
follicles (2-10mm), as well as those 2- 5mm, will be possible as these numbers will be
recorded separately. The total between the two ovaries (2- 10mm) will be considered the
AFC. The volume of each ovary will be calculated by measuring the three perpendicular
diameters and applying the formula for an ellipsoid: (L x H x W x π/6). Data will be
entered directly onto scannable datasheets. Examination will also determine whether
cysts/other abnormalities exist and provide images to document number and type of
abnormalities. Clinical alerts will be generated for ovarian cysts of greater than 3cm
diameter or solid adnexal masses of any size. Dr. Huddleston will be responsible for
relaying information about clinical alerts to patients and physicians.
5. Body composition: Total body water (TBW) and extracellular water (ECW) volumes will be
determined by bioimpedance spectroscopy (Intermed Inc, Melbourne Australia) at baseline,
16 and 32 weeks. Subjects will also be weighed at each visit. We will also do waist and
hip measurements at baseline, 16 and 32 weeks .
6. Blood pressure (BP) and heart rate (HR): These will be measured at each visit in the
morning after 10 minutes of rest in the sitting position using an automated
oscillometric device (Dinamap, Critikon Inc) programmed to obtain 3 readings within 3
minutes, and then will calculate average daily pressure
j. Questionnaires: Participants will complete the following questionnaires per the schedule
specified in Table 1. Questionnaires tap psychological experience, health and eating
behavior, and adherence.
