Role of Prostaglandins on Niacin-Induced Flushing
Information source: Eastern Virginia Medical School
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Flushing
Intervention: Niacin and aspirin (Drug)
Phase: N/A
Status: Completed
Sponsored by: Eastern Virginia Medical School Official(s) and/or principal investigator(s): Aaron I Vinik, MD, PhD, Principal Investigator, Affiliation: Eastern Virginia Medical School, Strelitz Diabetes Center
Summary
This study will focus on investigating the nicotinic acid stimulated release of
prostaglandin D2 in normal controls. In subsequent studies, the investigators would like to
further explore this pathway in people with type 2 diabetes. Enhanced blood flow (or
flushing) may be compromised or exaggerated in type 2 diabetes particularly in those with
impairment of autonomic function measured as the respiratory heart rate variability (HRV) of
different frequencies reflecting the balance between the sympathetic and parasympathetic
nervous systems. The investigators hypothesize that the vasodilatory effects induced by
nicotinic acid will be different in glabrous and hairy skin and that autonomic imbalance may
alter the response.
Clinical Details
Official title: Exploring the Role of Prostaglandin D2 and the DP1 Receptor on Nicotinic Acid Induced Flushing
Study design: Observational Model: Cohort, Time Perspective: Prospective
Primary outcome: The primary efficacy measures are skin perfusion measurements and neurological measures.
Secondary outcome: Secondary measures include blood chemistries
Detailed description:
The investigators propose that nicotinic acid (NA) stimulates release of prostaglandin D2
(PGD2). To fully understand this mechanism, the investigators will examine the systemic
release of PGD2 and skin blood flow using laser Doppler (LDF) on the upper and lower limbs
of healthy control subjects. The investigators will quantify and establish the effects of
oral nicotinic acid (NiaspanĀ®) given alone and in combination with aspirin on:
1. skin blood flow using laser Doppler (LDF) of glabrous and hairy skin of the forearm of
healthy subjects
2. the severity and intensity of flushing using a visual analog scale, FAST tool, and
whether aspirin is able to block the flushing response
3. the impact on sympathetic/parasympathetic balance using the various frequencies of
heart rate variability (HRV) which reflect the contribution of the different divisions
of the autonomic nervous system (ANS)
4. circulating levels of PGD2 and other neuropeptides to determine other mediators of the
flushing response. This will allow us to conclude whether this pathway is intact and
explore other non-DP1 vasodilatory mechanisms.
5. Langerhans cell density in epidermis and microvasculature using immunohistochemistry of
Langerin (measured as CD1a) in 3 mm skin biopsies of volar and hairy surfaces of the
forearm and hairy surface of the lateral aspect of proximal lower limb. To date, there
is very little known about the density or distribution of Langerhans cells. The PGD2
receptor DP1 will be examined for its content in the epidermis using
immunohistochemistry or RTPCR.
Eligibility
Minimum age: 30 Years.
Maximum age: 80 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
Healthy controls ages 30-80
Exclusion Criteria:
1. Presence of type 1 diabetes or type 2 diabetes
2. Presence of clinically significant neuropathy, (Dyck stage >2b) defined by abnormal
neurologic testing (neurologic physical exam, nerve conduction, autonomic and
quantitative sensory tests)
3. History of major macrovascular events such as myocardial infarction or stroke within
the past 3 months
4. Participation in another clinical trial concurrently or within 30 days prior to entry
into this study.
5. Uncontrolled or untreated hypothyroidism as evidenced by TSH concentrations >4. 8
uU/ml
6. Other serious medical conditions which, in the opinion of the investigator, would
compromise the subject's participation in the study, including sensitivity to aspirin
7. Abnormalities of liver function defined as any liver enzymes (AST, ALT, SGPT, SGOT)
greater than 3 times the upper limit of normal
8. History of NYHA Class IV congestive heart failure.
9. Allergy to Niaspan or aspirin
10. Use of drugs known to affect prostaglandin metabolism such as angiotensin converting
enzyme inhibitors (ACE) inhibitors and angiotensin receptor blockers (ARBs) will be
allowed with stable use for 3 months.
11. Pregnancy or breastfeeding
12. History of peptic ulcer disease
13. Current history of smoking
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Locations and Contacts
Eastern Virgnia Medical School, Strelitz Diabetes Center, Norfolk, Virginia 23510f, United States
Additional Information
Starting date: March 2009
Last updated: March 9, 2010
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