Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT02872584 |
| Other study ID # |
0134-16-RMB CTIL |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
N/A
|
| First received |
August 16, 2016 |
| Last updated |
August 18, 2016 |
| Start date |
September 2016 |
| Est. completion date |
September 2018 |
Study information
| Verified date |
August 2016 |
| Source |
Rambam Health Care Campus |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
Israel: Ministry of Health |
| Study type |
Observational
|
Clinical Trial Summary
Free fatty acid index will be measured in patients before and 1 month after high dose
prednisone.
Description:
Serum Free Fatty Acids Desaturase Activity Indices in Sera of Patients with Pemphigus and
Bullous Pemphigoid on Long-term High-dose Corticosteroid Treatment
1.1 BACKGOUND & STUDY RATIONALE Chronic exposure to glucocorticoids exerts profound effects
on subcutaneous and visceral adipose tissues, and may induce both lipolysis and lipogenesis
[1].
In acute conditions (such as stress) glucocorticoids increase whole body lipolysis, and free
fatty acid production and turnover. However, in chronic glucocorticoid excess conditions
(such as Cushing's syndrome), this acute induction of systemic lipolysis is not sustained,
and actually decreases. Moreover, glucocorticoids may act synergistically with insulin to
upregulate lipogenesis, and increase triglycerides storage, mainly in the liver and visceral
adipose tissue [2, 3]
Increased subcutaneous fat mass is a hallmark of Cushing's syndrome and could potentially be
mediated through the activation of lipogenesis. We have recently published a study that
found an upregulation of free fatty acids synthesis and desaturases genes and triglyceride
synthesis genes in subcutaneous adipose tissue from subjects with Cushing's disease, further
supporting the hypothesis that lipogenesis is activated in these tissues via the
transcriptional activation of fatty acid synthesis and triglyceride synthesis [4]. In
parallel, we saw higher levels of lipolysis in adipose tissue explants from Cushing's
disease patients [4].
In general, serum free fatty acids composition is influenced by dietary fat intake,
desaturating enzymes activity (in subcutaneous and visceral adipose tissues, and liver),
insulin resistance and lifestyle factors such as physical activity, and obesity [5, 6, 7].
However, fasting serum free fatty acids are not directly derived from nutritional intake,
but primarily originate from adipose tissue storages [8, 9] Desaturase indices, estimated as
product-to-precursor fatty acid ratios, are employed in epidemiological studies. Desaturase
activity indices were estimated according to the following: Stearoyl-CoA desaturase-16
(SCD-16) = 16:1(n-7) / 16:0, Stearoyl-CoA-desaturase-18 (SCD-18) = 18:1(n-9) / 18:0,
Delta-5-desaturase (D6D) = 20:3(n-6) / 18:2 (n-6), and Delta-5-desaturase (D5D) = 20:4(n-6)
/ 20:3 (n-6).
Estimated SCD-16, SCD-18, and D5D activity ratios were found to be correlated between
fasting serum free fatty acids and subcutaneous adipose tissue triglycerides [10]. Moreover,
the subcutaneous adipose tissue estimated SCD-16, and SCD-18 activity ratios, were
significantly correlated with SCD gene expression in this tissue [11].
Long-term effects of glucocorticoids on serum fasting free fatty acids composition and
desaturase indices were not studied. Our goal in this study is to examine whether there are
significant changes in estimated serum free fatty acids desaturase indices and in total free
fatty acids and glycerol after long-term glucocorticoid therapy.
1.2 STUDY OBJECTIVES 1.2.1 Primary objective The primary objective of this study is to
compare desaturase activity indices in sera of patients with pemphigus and bullous
pemphigoid, collected before, and one month after the initiation of high-dose oral
corticosteroid treatment.
Secondary objectives The secondary objectives are to examine the changes in weight,
waist/hip ratio, insulin resistance as reflected by the HOMA-IR model, and fasting lipid
profiles, over one month of high-dose oral corticosteroid treatment.
1.3 STUDY DESIGN This is a single-center prospective cohort study.
1.3.1 Study population About 20 consecutive eligible patients diagnosed with pemphigus or
bullous pemphigoid, who are planned to be placed on a high dose oral corticosteroid regimen
(equivalent to 0.5mg/kg/day or more of prednisone) for at least one month, will be
recruited.
1.3.2 Study duration Total duration of the study is expected to be 10 months.
1.4 STUDY METHODS For each patient, blood samples will be collected before, and one month
after the initiation of high-dose oral corticosteroids. Serum samples will be collected in
the morning after overnight fasting of approximately 12 hours.
Each blood sample will be assessed for the following:
- Serum free fatty acids levels, including: Palmitoleic Acid (16:1(n-7)), Palmitic Acid
(C16:0), Oleic Acid (C18:1(n-9)), Stearic Acid (C18:0), Linoleic Acid (C18:2(n-6)),
Arachidonic Acid (C20:4(n-6)), and Dihomogamma Linolenic (C20:3(n-6)).
Free fatty acids Levels in serum will be determined using Gas Chromatography-Mass
Spectrometry (GC/MS) Stable Isotope Dilution Analysis kit.
- Fasting lipid profile: Total cholesterol, low-density lipoprotein (LDL), high-density
lipoprotein (HDL), Triglycerides (TG), and free glycerol.
- Fasting plasma glucose, plasma insulin, and glycated hemoglobin (HbA1c)
- Complete blood count
- Creatinine and Urea
- Albumin and total protein
- Liver enzymes: AST, ALT, GGT, ALP
- Thyroid hormones: TSH, FT4, FT3
Desaturase activity indices will be estimated according to the following:
- Stearoyl-CoA desaturase-16 (SCD-16) = 16:1(n-7) / 16:0
- Stearoyl-CoA-desaturase-18 (SCD-18) = 18:1(n-9) / 18:0
- Delta-5-desaturase (D6D) = 20:3(n-6) / 18:2 (n-6)
- Delta-5-desaturase (D5D) = 20:4(n-6) / 20:3 (n-6).
Insulin resistance will be estimated by HOMA-IR (fasting insulin (mU/l) × fasting glucose
(mmol/l)/22.5).
The following physical measurements will be taken at enrolment and one month later:
- Weight, Height (BMI)
- Waist and hip measurement (waist/hip ratio)
