Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05926115 |
| Other study ID # |
1006 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
March 4, 2023 |
| Est. completion date |
September 30, 2023 |
Study information
| Verified date |
June 2023 |
| Source |
Instituto de fertilidad humana, InSer |
| Contact |
Walter E Osorio, M.D |
| Phone |
+57 3002213567 |
| Email |
wosorio[@]inser.com.co |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The goal of this observational study is to know the prevalence of PCOS among economically
productive and reproductive age women from Medellín and the Valle de Aburrá, Colombia. The
main questions it aims to answer are:
1. What is the phenotypic distribution of PCOS detected in women seeking medical attention
as a requirement for employment in Medellín and the Valle de Aburrá, Colombia?
2. What is the effect of environmental factors, such as geographical location and diet, and
biological factors (such as obesity and ethnicity/race) on the prevalence and phenotype
of PCOS in this populatión?
Participants will undergo anthropometric measurements and physical examination for hirsutism,
acne, alopecia, acanthosis nigricans, and thyroid enlargement. During the initial visit, a
transvaginal or transabdominal pelvic ultrasonography will be performed. A sample of venous
blood will be collected in plain tubes for serum cryopreservation and for immediate glucose
estimation. Some participants will be rescheduled for a second evaluation visit for
additional assessment when they have a possible PCOs.
Description:
During the first visit, potential study participants, scheduled for routine occupational
pre-admission medical examination at Colmédicos Medical Centre, will be invited to
participate in the study. Eligible study participants will be counselled on the objectives of
the study and the study protocol and a copy of the consent form will be handed to them. A
confidential study register containing details of potential study participants (name, age,
height, weight, and contact) will be start on the first visit day. Informed written consent
will be obtained from each study participant before recruitment for the study in the
evaluation visit number one. All study participants personal data will be protected according
to the law (ley 1581de Colombia).
1. Evaluation Visit #1:
After obtaining an informed consent, data will be collected from each study participant
using a standard format in a clinical report form (CRF) for uniform data collection from
all participants. Each CRF will bear a unique serial identification number and will be
written in the local language. The CRF will be filled by a trained researcher (including
the PI, co-investigators and medically trained research assistants). All CRF will be
checked for missing data within 24 hours of completion, and any missing data will be
detected and collected immediately. At no time, will the study personnel have access to
the participant´s medical occupational records, following the restrictions defined in
the colombian legislation (resolution 2346 de 2007, R 1918 de 2011).
Each participant will undergo anthropometric measurements (weight, height, waist
circumference and hip circumference) and physical examination for hirsutism, acne,
alopecia, acanthosis nigricans, and thyroid enlargement. Participants with an initial
hirsutism (mFG) score of 4 or more (≥ 4) will be re-assessed by a physician. During the
initial visit at Colmédicos, a transvaginal or transabdominal pelvic ultrasonography
will be performed in all participants, based on the sexual history and consent form by
trained gynecologists who are part of study investigators. A transvaginal ultrasound is
the accepted and validated method to assess the ovarian morphology in the study of
patients with PCOS.
After an overnight fast of at least 6 hours (ideally), a 18 ml sample of venous blood
will be collected from each study participant (i.e., the basal fasting sample). About 12
ml of the venous blood will be collected in plain tubes for serum cryopreservation and
subsequent analysis, and the remainder in plain tubes for immediate glucose estimation
in serum.
2. Sample Processing:
The initial blood specimens will be labeled with the participant´s unique ID number,
time and date of blood collection and date of last menstrual period (LMP). The samples
will be obtained by trained laboratory personnel from Colmédicos medical center during
the morning hours (08:00 to 10:00 hours), regardless of the participant's menstrual
cycle. Participants with oligomenorrhoea or amenorrhoea will have a urine pregnancy done
test prior to blood sampling.
At Colmédicos laboratory, the blood samples will be separated into serum, plasma and
whole blood by centrifugation for 20 minutes at 3000 rpm. The biological specimens will
be stored, in small aliquots (of 1,25 ml), in 1.5 to 2.0 ml plastic containers (about 4
cryovials) able to withstand temperatures of -80 degrees centigrade. The aliquoted
samples will be sent to the ABAD Zona 2 SUR laboratory (Carrera 32 No. 2 Sur 47 local
9701) in dry ice containers by the laboratory's courier staff where they will be stored
at -20 degrees centigrade for a maximum of 3 months for processing. If necessary, for
longer storage, the samples will be transferred to the Inser Medellin laboratory and
stored at -80 degrees centigrade where they will remain in custody until their use or
final disposal according to the established institutional waste management protocol.
3. Hormonal & chemical analyses:
Samples for hormonal assay and the initial evaluation will be batched at regular
intervals for the analysis every week to provide the study participants with timely
results, allow classification of participants and minimize the impact of inter-assay
variability. In addition, this will allow us to timely contact participants who require
additional studies.
All participants will be evaluated in a uniform manner regardless of the phase of the
cycle in which they are.
4. Evaluating subjects with "Possible PCOS":
The cohort of participants who initially meet clinical features suggestive of PCOS
(i.e., HA, OA or PCOM, will be designated as "Possible PCOS", and will undergo the
following measurements in their samples:
1. In all "Possible PCOS" subjects TSH, prolactin (PRL), and 17-HP will be measured in
the basal serum samples as well as fasting glucose.
Note: All subjects diagnosed with PCOS should have a normal TSH, PRL, and 17-HP
(basally or after acute ACTH stimulation).
2. In women presenting clinically with HA+OA, if the TV-U/S performed demonstrates
PCOM the subject is classified as having PCOS phenotype A (HA+OA+PCOM); if not the
subject is classified as having PCOS phenotype B (HA+OA).
3. Subjects presenting clinically with HA only will return during the luteal phase
(days 21-24) of their menstrual cycle for a serum progesterone (P4) level. Subjects
with HA who demonstrate OA (i.e., luteal P4 < 3 ng/mL) will be classified as having
PCOS phenotype A if they have PCOM by TV-U/S (HA+OA+PCOM) or PCOS phenotype B
(HA+OA) if they do not exhibit PCOM. HA subjects who also demonstrate PCOM, but no
OA (i.e., luteal P4 ≥3 ng/mL) will be classified as PCOS phenotype C. Participants
with HA, but no PCOM or OA will be classified as having isolated HA.
4. Subjects presenting clinically with OA only, their basal serum samples will be
assayed for androgen levels (total [TT] and free testosterone [FT],
dehydroepiandrosterone sulphate [DHEAS], and androstenedione [A4]). Subjects with
OA who demonstrate HA (i.e., elevated androgen levels) will be classified as having
PCOS phenotype A if they have PCOM by TV-U/S (HA+OA+PCOM) or PCOS phenotype B
(HA+OA) if they do not exhibit PCOM. OA subjects who also demonstrate PCOM, but no
HA (i.e., normal androgen levels) will be classified as PCOS phenotype D.
Participants with OA, but no PCOM or HA will be classified as having isolated OA.
5. Subjects presenting with PCOM by TV-U/S will return during the luteal phase (days
22-24) of their menstrual cycle for a serum progesterone (P4) level and their basal
serum samples will be assayed for androgen levels (total [TT] and free testosterone
[FT], dehydroepiandrosterone sulphate [DHEAS], and androstenedione [A4]). Subjects
with PCOM who demonstrate OA (i.e., luteal P4 < 3 ng/mL) will be classified as
having PCOS phenotype D. If they also demonstrate HA (i.e., elevated androgen
levels) (HA+OA+PCOM) will be classified as having PCOS phenotype A. PCOM subjects
who also demonstrate HA, but no OA (i.e., luteal P4 ≥3 ng/mL) will be classified as
PCOS phenotype C. Participants with PCOM, but no HA or OA will be classified as
having isolated PCOM.
5. Diagnosing PCOS:
Related or mimicking disorders will be excluded using history, physical examination, and
serum TSH, PRL and 17-OHP. Study participants with a basal 17-OHP >2 ng/ml (or 200
ng/dl) will undergo a repeat 17-OHP measurement in the follicular phase and if the
17-OHP is still > 2ng/mL an acute adrenocorticotrophic hormone (ACTH) stimulation test
will be performed to exclude non-classical congenital adrenal hyperplasia (NCAH). We
estimate, considering our previous data, that approximately 6% of subjects screened will
require an acute ACTH stimulation test.
Overall, PCOS will be diagnosed when subjects present with either HA+OA+PCOM (phenotype
A), HA+OA (phenotype B), HA+PCOM (phenotype C) and OA+PCOM (phenotype D) and demonstrate
normal levels of TSH (0,37 to 4,7 mUI/L), PRL (<25 ng/mL) and 17-OHP, per our diagnostic
algorithm.
6. Evaluation visit #2:
In the following cases subjects will be rescheduled for a second evaluation visit
(evaluation visit #2) for additional assessment:
1. All subjects with PCOS will be scheduled for a return visit to undergo a 2-hour 75g
oral glucose tolerance test (OGTT) with 3 ml of venous blood collected in serum
tubes at 0 minutes and at 120 minutes post-glucose load. Glucose and insulin (from
serum tubes) levels will be assessed at 0 and 120 min.
2. Participants will be reevaluated during the follicular phase of the menstrual cycle
(between day 1 and 5):
i. With a repeat ultrasound in case there is a dominant follicle (≥ 10 mm) or an ovarian
cyst at the initial ultrasound evaluation.
ii. A repeat 17-hydroxyprogesterone (17-OHP) measurement in the event the initial 17-OHP
is >2 ng/mL and was obtained during the luteal phase according to menstrual history.
Approximately 50% of Participants evaluated in luteal phase are expected to have a
17-OHP >2 ng/mL.
iii. An acute intravenous (iv) ACTH-1-24 (0.25 mg) stimulation test, if the initial and
repeat 17-OHP obtained during the follicular phase, according to menstrual history, is >
2 ng/mL.
7. Reassessing hormonal levels:
At the completion of the study, a repeat analysis of the samples for androgen levels in all
PCOS subjects and a group of 'super-controls' (30 controls) will be performed at a reference
laboratory. A fasting glucose level also be analyzed in a group of super controls (100
controls). Genetic analysis could be performed depending on the availability of financial
support in a reference laboratory.
