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
Intervention: Hydrocortisone (Solucortef); Insulin pump (Medtronic)
Intervention description: 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)
Intervention MeSH terms: Hydrocortisone; Hydrocortisone hemisuccinate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: Glucocorticoids; Adrenal Insufficiency; Congenital Adrenal Hyperplasia (CAH); Adrenal

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
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

          -  Patients with known classic CAH due to 21-hydroxylase deficiency as evidenced by
             hormonal and genetic testing

          -  Male or female patients 18 years or older

          -  Females must have a negative pregnancy test initially and at all visits. Sexually
             active females must be using a medically acceptable method of contraception.

          -  Patients with elevated adrenal androgens (defined as 17-OHP >1200 ng/dL and
             androstenedione >210 ng/dL)

          -  One or more co-morbidities:<TAB>

          -  Obesity [body mass index (BMI) greater than 30.0 kg/m(2)]

          -  Fatty liver disease; assessed by AST/ALT liver enzyme ratio (AST to ALT ratio <1 (11))
             liver ultrasound or MRI imaging (Steatosis score as previously described)

          -  Low insulin sensitivity; assessed by the Homeostasis Model Assessment Insulin
             Resistance (HOMA-IR) method [HOMA-IR = insulin (micro U/ml) times glucose (mmol/L)/
             22.5]. Elevated HOMA-IR index is defined as >2.6 in adults17.

          -  Osteopenia [bone mineral density by DEXA (at the spine, hip, or forearm) with T-score
             of -1 to -2.5) or osteoporosis (bone mineral density by DEXA (at the spine, hip, or
             forearm) with T-score of <-2.5] defined according to World Health Organization (WHO).

          -  Glucocorticoid-related gastrointestinal side effects (nausea, vomiting, dyspepsia,
             anorexia, gastritis, peptic ulcer disease and gastric bleeding)

        EXCLUSION CRITERIA:

          -  Co-morbid conditions requiring daily administration of medications that induce hepatic
             enzymes or interfere with the metabolism of glucocorticoids

          -  Females who are pregnant or lactating

          -  Patients on inhaled or oral steroids given for reasons other than treatment of CAH

          -  Women who have taken estrogen-containing oral contraceptive pills within 6 weeks of
             recruitment

          -  Patients who required stress dose glucocorticoids for an illness within 4 weeks of
             recruitment

          -  Patients who changed their glucocorticoid agent within 3 months of recruitment

          -  Patients who underwent bilateral adrenalectomy

          -  Co-morbid conditions that could interfere with the ability to comply to the protocol