Comparison of Cortisol Pump With Standard Treatment for Congenital Adrenal Hyperplasia

NCT01859312 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 13012113-CH-0121
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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
• Men and women 18 years of age or older with classic congenital adrenal hyperplasia (21-Hydroxylase deficiency)
• High adrenal androgens in the blood, and
• One or more of the following conditions: obesity, fatty liver, risk for diabetes, low bone mass, inability to tolerate cortisol pills
• Pregnancy
• Breast feeding
• Use of inhaled or oral steroids for diseases other than CAH
• Use of estrogen-containing birth control pills
• Use of medicines that cross-react with hydrocortisone
• Use of stress dose steroids for illness during the last 30 days prior to joining the study

Conditions

Adrenal Insufficiency; Excess Androgen; Congenital Adrenal Hyperplasia (CAH)

Keywords

Glucocorticoids; Adrenal Insufficiency; Congenital Adrenal Hyperplasia (CAH); Adrenal

Outcome Measures

Primary Outcomes (2)

• Number of Patients With 17-OHP Levels Equal or Below 1,200 ng/dL at 0700

  17-OHP (17-hydroxyprogesterone) is a laboratory blood test to test for congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency

  At baseline

• Number of Patients With 17-OH Progesterone Levels Equal or Below 1,200 ng/dL at 0700

  17-OHP (17-hydroxyprogesterone) is a laboratory blood test to test for congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency

  At 6 months

Secondary Outcomes (42)

• Participants Mean Level of 17-OHP at 0700

  At baseline

• Participants Mean Level of 17-OHP at 0700

  At 6 months

• Participants Mean Level of 17-OHP Area Under the Curve (AUC) - 24 Hours

  At baseline

• Participants Mean Level of 17-OHP Area Under the Curve (AUC) - 24 Hours

  At 6 months

• Participants Mean Level of 17-OHP Area Under the Curve (AUC) - Daytime (0700-1500)

  At baseline

Study Arms (1)

Continuous Subcutaneous Hydrocortisone Infusion

EXPERIMENTAL

Enrolled participants with congenital adrenal hyperplasia (CAH) received continuous subcutaneous hydrocortisone (Solucortef) infusion (CSHI) via insulin pump (Medtronic) (MMT-722Na) to achieve near-physiologic cortisol replacement therapy. Participants were their own controls; participant's baseline outcomes/lab values while on conventional glucocorticoid therapy were compared to outcomes/lab values after 6 months of treatment using CSHI via insulin pump.

Drug: Hydrocortisone (Solucortef); Device: Insulin pump (Medtronic)

Interventions

Hydrocortisone (Solucortef) DRUG

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.

Also known as: CSHI

Continuous Subcutaneous Hydrocortisone Infusion

Insulin pump (Medtronic) DEVICE

Continuous subcutaneous hydrocortisone infusion (CSHI) via Medtronic insulin pump (MMT-722NA)

Also known as: CSHI

Continuous Subcutaneous Hydrocortisone Infusion

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institutes of Health Clinical Center (CC): lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (5)

• Debono M, Ghobadi C, Rostami-Hodjegan A, Huatan H, Campbell MJ, Newell-Price J, Darzy K, Merke DP, Arlt W, Ross RJ. Modified-release hydrocortisone to provide circadian cortisol profiles. J Clin Endocrinol Metab. 2009 May;94(5):1548-54. doi: 10.1210/jc.2008-2380. Epub 2009 Feb 17.

  PMID: 19223520 BACKGROUND

• Finkielstain GP, Kim MS, Sinaii N, Nishitani M, Van Ryzin C, Hill SC, Reynolds JC, Hanna RM, Merke DP. Clinical characteristics of a cohort of 244 patients with congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2012 Dec;97(12):4429-38. doi: 10.1210/jc.2012-2102. Epub 2012 Sep 18.

  PMID: 22990093 BACKGROUND

• Arlt W, Willis DS, Wild SH, Krone N, Doherty EJ, Hahner S, Han TS, Carroll PV, Conway GS, Rees DA, Stimson RH, Walker BR, Connell JM, Ross RJ; United Kingdom Congenital Adrenal Hyperplasia Adult Study Executive (CaHASE). Health status of adults with congenital adrenal hyperplasia: a cohort study of 203 patients. J Clin Endocrinol Metab. 2010 Nov;95(11):5110-21. doi: 10.1210/jc.2010-0917. Epub 2010 Aug 18.

  PMID: 20719839 BACKGROUND

• Nella AA, Mallappa A, Perritt AF, Gounden V, Kumar P, Sinaii N, Daley LA, Ling A, Liu CY, Soldin SJ, Merke DP. A Phase 2 Study of Continuous Subcutaneous Hydrocortisone Infusion in Adults With Congenital Adrenal Hyperplasia. J Clin Endocrinol Metab. 2016 Dec;101(12):4690-4698. doi: 10.1210/jc.2016-1916. Epub 2016 Sep 28.

  PMID: 27680873 RESULT

• Mallappa A, Nella AA, Sinaii N, Rao H, Gounden V, Perritt AF, Kumar P, Ling A, Liu CY, Soldin SJ, Merke DP. Long-term use of continuous subcutaneous hydrocortisone infusion therapy in patients with congenital adrenal hyperplasia. Clin Endocrinol (Oxf). 2018 Oct;89(4):399-407. doi: 10.1111/cen.13813. Epub 2018 Aug 8.

  PMID: 30003563 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Adrenal Insufficiency; Hyperandrogenism; Adrenal Hyperplasia, Congenital

Interventions

Hydrocortisone

Condition Hierarchy (Ancestors)

Adrenal Gland Diseases; Endocrine System Diseases; 46, XX Disorders of Sex Development; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Adrenogenital Syndrome; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Gonadal Disorders; Genetic Diseases, Inborn; Steroid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Limitations and Caveats

All patients completed the study; according to medication and supply accountability, one patient was found to be partially non-compliant, the pump was disconnected approximately 30% of the time. When this patient was excluded, analysis were the same.

Results Point of Contact

• Title: Deborah P. Merke, MD, MS
• Organization: National Institute of Child Health and Human Development (NICHD)

DMerke@cc.nih.gov

301-496-0718

Study Officials

• Deborah P Merke, M.D.

  National Institutes of Health Clinical Center (CC)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2013
• First Posted: May 21, 2013
• Study Start: May 6, 2013
• Primary Completion: December 2, 2016
• Study Completion: December 2, 2016
• Last Updated: December 22, 2017
• Results First Posted: November 22, 2017

Record last verified: 2017-10-02

Locations

US (1)