Effects of Oral Glucosamine on Insulin and Blood Vessel Activity in Normal and Obese People
Condition: Obesity; Insulin Resistance
MeSH terms: Insulin Resistance
Study type: Interventional
Phase: Phase 1

Summary: 
      This study will examine whether glucosamine affects the way the body responds to insulin.
      Insulin is a hormone that causes the body to use glucose (sugar). Insulin does not work as
      well in overweight people, causing a condition called insulin resistance. Insulin also
      increases the flow of blood into muscle by opening inactive blood vessels. This study will
      test whether glucosamine, a nutritional supplement that many people take to treat arthritis,
      can cause or worsen insulin resistance or change how blood vessels react to insulin in normal
      weight and overweight people.

      Healthy normal weight and overweight volunteers between 21 and 65 years of age may be
      eligible for this study. Candidates will be screened with a brief physical examination,
      medical history, and blood and urine tests. After screening, participants will have three
      additional outpatient clinic visits for the following procedures:

      Visit 1

        -  Glucose clamp test to measure the body's response to insulin: For this procedure, a
           needle is placed in a vein of each arm, one for drawing blood samples, and one for
           infusing glucose and a potassium solution. The glucose is infused continuously during
           this 4-hour test and blood is drawn frequently to monitor glucose and insulin levels.
           After the test, blood glucose levels are monitored for another 2 hours to make sure they
           remain at an adequate level to prevent hypoglycemia (low blood sugar).

        -  Blood flow measurement: Blood flow in the brachial artery of the arm is measured to
           assess how many capillaries (very small blood vessels) are being used to supply
           nutrients and oxygen to the muscle in the forearm. This test is done at the same time as
           the glucose clamp test. Blood flow is measured using a technique called contrast
           ultrasound. A small amount of contrast agent consisting of gas-filled bubbles the size
           of red blood cells is infused over 10 minutes through one of the catheters placed in the
           vein for the glucose clamp test. The contrast agent is infused twice, once at the
           beginning of the glucose clamp test and once at the end of the test. The contrast
           material creates a signal in response to ultrasound that provides information about the
           distribution of capillaries in the forearm.

        -  Assignment to medication group: Participants are randomly assigned to take either
           glucosamine or placebo three times a day by mouth for 6 weeks. At the end of the 6
           weeks, no study drug is taken for 1 week, and then participants "cross-over"
           medications, those who took glucosamine for the first 6 weeks take placebo for the next
           6 weeks and vice versa.

      Visits 2 and 3

      For these visits, the glucose clamp test and blood flow measurements are repeated. Visit 2 is
      scheduled at the end of the first 6-week treatment period, and Visit 3 is scheduled at the
      end of the second 6-week treatment period.
    

Detailed description: 
      Glucosamine is a popular over-the-counter nutritional supplement that many people use for the
      treatment of osteoarthritis. Intravenous administration of glucosamine to animals or humans
      causes significant metabolic insulin resistance and vascular endothelial dysfunction.
      Moreover, experiments with various cell lines have implicated elevated glucosamine levels in
      the development of insulin resistance. However, there are no published studies examining the
      potential effects of oral glucosamine administration to modulate insulin sensitivity or
      capillary recruitment in humans. This is a significant concern because insulin resistance and
      vascular dysfunction contribute importantly to major public health problems including
      diabetes, obesity, hypertension, and cardiovascular diseases. Normal healthy volunteers and
      obese insulin resistant subjects will be enrolled in a randomized double-blind,
      placebo-controlled, crossover study to evaluate the effects of oral glucosamine to modulate
      insulin sensitivity and insulin-stimulated capillary recruitment. The reference standard
      hyperinsulinemic isoglycemic glucose clamp technique will be used to assess insulin
      sensitivity before treatment, after placebo or oral glucosamine (500 mg p.o. TID for 6
      weeks), and after completion of the crossover. In addition, insulin-stimulated capillary
      recruitment will be measured at the same time as the glucose clamp studies by using the
      ultrasound microbubble contrast technique to assess blood flow in the brachial artery and
      capillary recruitment in forearm skeletal muscle in response to hyperinsulinemia. Finally,
      plasma glucosamine levels will be measured just prior to each glucose clamp study using an
      HPLC method. The results of this study will determine if oral glucosamine administration
      causes significant insulin resistance and impairment in insulin-stimulated capillary
      recruitment in healthy volunteers or worsens insulin resistance and capillary recruitment in
      obese subjects. In addition, our study will provide important information about how plasma
      glucosamine levels change with commonly used oral doses of glucosamine.
    

Intervention name(s): Glucosamine Hydrochloride
Intervention type(s): Drug
Primary purpose: Treatment
Keywords: Diabetes; Insulin Resistance; Capillary Blood Flow; Osteoarthritis; Endothelial Dysfunction; Obesity; Healthy Volunteer; HV