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Comparison of Cortisol Pump With Standard Treatment for Congenital Adrenal Hyperplasia

This study has been completed.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) Identifier:
First received: May 17, 2013
Last updated: April 20, 2017
Last verified: December 2, 2016


  • 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.


- To compare the effectiveness of a cortisol pump with standard cortisol pill therapy for CAH.


- Men and women at least 18 years of age who have CAH (see more details in Eligibility section below).


  • 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


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

Condition Intervention Phase
Adrenal Insufficiency Excess Androgen Congenital Adrenal Hyperplasia (CAH) Drug: Hydrocortisone (Solucortef) Device: Insulin pump (Medtronic) Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Primary Purpose: Treatment
Official Title: A Pilot Study Assessing the Use of Continuous Subcutaneous Hydrocortisone Infusion in the Treatment of Congenital Adrenal Hyperplasia

Resource links provided by NLM:

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Percent of patients with 17-OH Progesterone levels equal or below 1,200 ng/dL at 8 a.m. [ Time Frame: 6 mos ]

Secondary Outcome Measures:
  • Percent of patients with hypertensive BP measurements [ Time Frame: 6 mos ]
  • Body composition measured by DEXA [ Time Frame: 6 mos ]
  • Weight and BMI [ Time Frame: 6 mos ]
  • Insulin resistance measured by HOMA-IR [ Time Frame: 6 mos ]
  • Change in percent of patients with androstenedione &amp; testosterone within the normal range at 8 a.m. [ Time Frame: 6 mos ]
  • Fatigue and quality of life. [ Time Frame: 6 mos ]

Enrollment: 8
Study Start Date: May 6, 2013
Study Completion Date: December 2, 2016
Primary Completion Date: December 2, 2016 (Final data collection date for primary outcome measure)
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.

Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
  • 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)


  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01859312

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institutes of Health Clinical Center (CC)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Principal Investigator: Deborah P Merke, M.D. National Institutes of Health Clinical Center (CC)
  More Information

Additional Information:
Responsible Party: National Institutes of Health Clinical Center (CC) Identifier: NCT01859312     History of Changes
Other Study ID Numbers: 130121
Study First Received: May 17, 2013
Last Updated: April 20, 2017

Keywords provided by National Institutes of Health Clinical Center (CC):
Adrenal Insufficiency
Congenital Adrenal Hyperplasia (CAH)

Additional relevant MeSH terms:
Adrenal Insufficiency
Adrenal Hyperplasia, Congenital
Adrenogenital Syndrome
Adrenocortical Hyperfunction
Pathologic Processes
Adrenal Gland Diseases
Endocrine System Diseases
Disorders of Sex Development
Urogenital Abnormalities
Congenital Abnormalities
Genetic Diseases, Inborn
Steroid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Metabolic Diseases
Gonadal Disorders
46, XX Disorders of Sex Development
Hydrocortisone 17-butyrate 21-propionate
Cortisol succinate
Hydrocortisone acetate
Epinephryl borate
Anti-Inflammatory Agents
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents processed this record on September 21, 2017