Role of Prostaglandins on Niacin-Induced Flushing

This study has been completed.
Sponsor:
Collaborator:
Abbott
Information provided by:
Eastern Virginia Medical School
ClinicalTrials.gov Identifier:
NCT00930839
First received: June 30, 2009
Last updated: March 9, 2010
Last verified: March 2010
  Purpose

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.


Condition Intervention
Flushing
Drug: Niacin and aspirin

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Exploring the Role of Prostaglandin D2 and the DP1 Receptor on Nicotinic Acid Induced Flushing

Resource links provided by NLM:


Further study details as provided by Eastern Virginia Medical School:

Primary Outcome Measures:
  • The primary efficacy measures are skin perfusion measurements and neurological measures. [ Time Frame: 30 minutes after administration of Niacin ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Secondary measures include blood chemistries [ Time Frame: 15-30 min serial measurements ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples Without DNA

Skin biopsies and serum


Enrollment: 30
Study Start Date: March 2009
Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Controls
Normal, healthy controls, males and females, ages 30-80
Drug: Niacin and aspirin
1000 mg Niacin, 325 mg aspirin
Other Names:
  • Niaspan
  • Nicotinic acid

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 (Niaspan®) 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

Ages Eligible for Study:   30 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Normal, healthy control subjects, males and females, ages 30-80

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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  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00930839

Locations
United States, Virginia
Eastern Virgnia Medical School, Strelitz Diabetes Center
Norfolk, Virginia, United States, 23510f
Sponsors and Collaborators
Eastern Virginia Medical School
Abbott
Investigators
Principal Investigator: Aaron I Vinik, MD, PhD Eastern Virginia Medical School, Strelitz Diabetes Center
  More Information

No publications provided

Responsible Party: Aaron I. Vinik, MD, PhD, Eastern Virginia Medical School, Strelitz Diabetes Center
ClinicalTrials.gov Identifier: NCT00930839     History of Changes
Other Study ID Numbers: A10-597
Study First Received: June 30, 2009
Last Updated: March 9, 2010
Health Authority: United States: Institutional Review Board

Keywords provided by Eastern Virginia Medical School:
Niacin
Prostaglandin D2
Flushing
Nicotinic acid stimulated release of prostaglandin D2

Additional relevant MeSH terms:
Flushing
Signs and Symptoms
Aspirin
Niacin
Nicotinic Acids
Niacinamide
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Central Nervous System Agents
Hypolipidemic Agents
Antimetabolites
Lipid Regulating Agents
Vasodilator Agents

ClinicalTrials.gov processed this record on August 28, 2014