Trial record 5 of 29 for:    Open Studies | "Adrenal Insufficiency"

Comparison of Cortisol Pump With Standard Treatment for Congenital Adrenal Hyperplasia

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01859312
First received: May 17, 2013
Last updated: March 14, 2014
Last verified: January 2014
  Purpose

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

Condition Intervention Phase
Adrenal Insufficiency
Excess Androgen
Congenital Adrenal Hyperplasia (CAH)
Drug: Hydrocortisone (Solucortef)
Device: Insulin pump (Medtronic)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percent of patients with hypertensive BP measurements [ Time Frame: 6 mos ] [ Designated as safety issue: No ]
  • Body composition measured by DEXA [ Time Frame: 6 mos ] [ Designated as safety issue: No ]
  • Weight and BMI [ Time Frame: 6 mos ] [ Designated as safety issue: No ]
  • Insulin resistance measured by HOMA-IR [ Time Frame: 6 mos ] [ Designated as safety issue: No ]
  • Change in percent of patients with androstenedione & amp; testosterone within the normal range at 8 a.m. [ Time Frame: 6 mos ] [ Designated as safety issue: No ]
  • Fatigue and quality of life. [ Time Frame: 6 mos ] [ Designated as safety issue: No ]

Estimated Enrollment: 8
Study Start Date: May 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Hydrocortisone (Solucortef)
    N/A
    Device: Insulin pump (Medtronic)
    N/A
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 (whole body bone mineral density T-score of -1 to -2.5) or osteoporosis (whole body bone mineral density T-score < -2.5)
  • 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
  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 ClinicalTrials.gov identifier: NCT01859312

Contacts
Contact: Aikaterini Nella, M.D. (301) 496-6437 nellaa@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Deborah P Merke, M.D. National Institutes of Health Clinical Center (CC)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT01859312     History of Changes
Other Study ID Numbers: 130121, 13-CH-0121
Study First Received: May 17, 2013
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

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

Additional relevant MeSH terms:
Adrenal Insufficiency
Addison Disease
Adrenal Hyperplasia, Congenital
Adrenogenital Syndrome
Adrenocortical Hyperfunction
Hyperplasia
Adrenal Gland Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Disorders of Sex Development
Urogenital Abnormalities
Congenital Abnormalities
Genetic Diseases, Inborn
Steroid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Metabolic Diseases
Gonadal Disorders
Pathologic Processes
Cortisol succinate
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone
Hydrocortisone-17-butyrate
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Dermatologic Agents

ClinicalTrials.gov processed this record on July 22, 2014