Comparison of Cortisol Pump With Standard Treatment for Congenital Adrenal Hyperplasia
Condition: Adrenal Insufficiency; Excess Androgen; Congenital Adrenal Hyperplasia (CAH)
MeSH terms: Adrenal Hyperplasia, Congenital; Adrenogenital Syndrome; Adrenal Insufficiency; Adrenocortical Hyperfunction; Hyperplasia
Study type: Interventional
Phase: Phase 2

Summary: 
      Background:

        -  Congenital adrenal hyperplasia (CAH) is a genetic disorder of the adrenal gland. The
           adrenal gland is located in the abdomen and produces small amounts of hormones such as
           cortisol, aldosterone, and androgen. These hormones help control blood pressure, protect
           the body, and maintain good health, especially during development. People with CAH do
           not make enough cortisol and aldosterone, and make too much androgen. This can lead to
           serious medical problems. The standard treatment is to take pills that mimic the effects
           of cortisol and aldosterone. However, treatment with pills can have long-term side
           effects because of the higher doses needed, and may not work well for some people.

        -  A possible new treatment for CAH is to use a pump to deliver cortisol under the skin.
           Similar pumps are often used to give insulin to people with diabetes. Researchers think
           that a cortisol pump might be able to help the body use the cortisol more effectively
           than taking pills. They want to compare the results of a cortisol pump and standard pill
           treatments for CAH.

      Objectives:

      - To compare the effectiveness of a cortisol pump with standard cortisol pill therapy for
      CAH.

      Eligibility:

      - Men and women at least 18 years of age who have CAH (see more details in Eligibility
      section below).

      Design:

        -  This study will involve four inpatient hospital stays at the National Institutes of
           Health in Bethesda, MD over 6 months (spaced 2 months apart). The first and last stays
           will last about 5 days. The second and third stays will last about 3 days.

        -  Participants will be screened with a physical exam and medical history. Blood and urine
           samples will be collected.

        -  At the first study visit, participants will provide regular blood and urine samples.
           They will also have imaging studies. These studies will look at the bones, fat, and
           muscles in the abdomen and pelvis.

        -  Participants will receive a cortisol pump during the first visit. They will be shown how
           to use the pump. They will also learn what to do, if they need to take extra "stress
           dose" cortisol pills.

        -  At the second and third visits, the cortisol dose given with the pump will be adjusted
           as needed. Blood and urine samples will also be collected. No imaging studies are
           scheduled for these visits.

        -  The last study visit will have the same tests as the first visit. Participants will be
           offered the chance to continue with the pump treatment for 1 more year, or go back to
           their standard pill treatment.

      Study type: Interventional non-randomized trial

      Official title: A Pilot Study Assessing the use of Continuous Subcutaneous Hydrocortisone
      Infusion In the Treatment of Congenital Adrenal Hyperplasia

      Estimated enrollment: 8

      Study Start Date: May 2013

      Estimated Study Completion Date: December 2016

      Sponsoring Institute: National Institute of Child Health and Human Development

      <TAB>ELIGIBILITY

      Inclusion criteria

        1. Men and women 18 years of age or older with classic congenital adrenal hyperplasia
           (21-Hydroxylase deficiency)

        2. High adrenal androgens in the blood, and

        3. One or more of the following conditions: obesity, fatty liver, risk for diabetes, low
           bone mass, inability to tolerate cortisol pills

      Exclusion criteria

        1. Pregnancy

        2. Breast feeding

        3. Use of inhaled or oral steroids for diseases other than CAH

        4. Use of estrogen-containing birth control pills

        5. Use of medicines that cross-react with hydrocortisone

        6. Use of stress dose steroids for illness during the last 30 days prior to joining the
           study
    

Detailed description: 
      Congenital adrenal hyperplasia (CAH) is a common genetic endocrine disorder, with
      21-hydroxylase enzyme deficiency accounting for 95% of the cases. 21-hydroxylase deficiency
      presents with a spectrum of clinical manifestations ranging from salt-wasting and
      virilization of female neonates (classic CAH) to symptomatic (precocious puberty, short
      stature, acne) or asymptomatic hyperandrogenemia (non-classic CAH). Classic CAH is
      characterized by impaired cortisol and mineralocorticoid biosynthesis, which triggers
      adrenocorticotropic hormone (ACTH) hyper-secretion and accumulation of adrenal androgens.
      Glucocorticoid treatment of patients with classic CAH focuses on cortisol replacement and
      prevention of the ACTH-driven androgen excess. Current conventional glucocorticoid treatment
      regimens (short or long-acting agents dosed once, twice or thrice daily) have failed to
      simulate physiological cortisol secretion and suppress adrenal androgen overproduction,
      without supraphysiologic replacement. Short-term overtreatment with glucocorticoids can lead
      to iatrogenic Cushing syndrome and long-term use has been associated with the development of
      obesity, visceral adiposity, insulin resistance and osteoporosis. Isolated case reports have
      provided evidence that continuous subcutaneous hydrocortisone infusion (CSHI) can mimic
      physiologic cortisol release and lead to improved CAH control at doses similar to or lower
      than the traditional treatment. This pilot study aims to test the hypothesis that
      difficult-to-treat adult patients with classic CAH will have better adrenal androgen control
      and improved CAH and glucocorticoid-related comorbidities, when they receive near-physiologic
      cortisol replacement therapy via CSHI compared to conventional glucocorticoid treatment. In
      addition, this study will provide information on the safety and tolerability of CSHI, and
      will generate data that will be used in the design of future pediatric studies.
    

Intervention name(s): Hydrocortisone (Solucortef); Insulin pump (Medtronic)
Intervention type(s): Drug; Device
Intervention description(s): Continuous subcutaneous hydrocortisone infusion (CSHI) via Medtronic insulin pump (MMT-722NA). Total daily hydrocortisone dose was calculated based on the patient's estimated cortisol clearance. Rates were established to achieve peak and trough concentrations within the normal circadian cortisol range.; Continuous subcutaneous hydrocortisone infusion (CSHI) via Medtronic insulin pump (MMT-722NA)
Other intervention name(s): CSHI; CSHI
Intervention MeSH terms: Hydrocortisone; Hydrocortisone hemisuccinate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Glucocorticoids; Adrenal Insufficiency; Congenital Adrenal Hyperplasia (CAH); Adrenal