Comparison of Cortisol Pump With Standard Treatment for Congenital Adrenal Hyperplasia
| Status: | Completed |
|---|---|
| Conditions: | Endocrine, Hematology |
| Therapuetic Areas: | Endocrinology, Hematology |
| Healthy: | No |
| Age Range: | 18 - 99 |
| Updated: | 12/24/2017 |
| Start Date: | May 6, 2013 |
| End Date: | December 2, 2016 |
A Pilot Study Assessing the Use of Continuous Subcutaneous Hydrocortisone Infusion in the Treatment of Congenital Adrenal Hyperplasia
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
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
- 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
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
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.
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.
- 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:
- 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
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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