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An Open Label, Multicenter Study Evaluating the Safety and Efficacy of Short Term (6 Weeks) Rosiglitazone Treatment in Patient's With Cushing's Disease

Phase 2
18 Years
65 Years
Not Enrolling
Cushing's Disease

Thank you

Trial Information

An Open Label, Multicenter Study Evaluating the Safety and Efficacy of Short Term (6 Weeks) Rosiglitazone Treatment in Patient's With Cushing's Disease



- To assess the effect of rosiglitazone on biochemical control in patients with newly
diagnosed ACTH-secreting pituitary tumor (Cushing disease).

- To assess the effect of this drug on a core biochemical parameter (24-hour urinary-free
cortisol) associated with disease progression.


- To assess the effect of this drug on corticotrophin (CRH)-stimulated pituitary tumor
ACTH secretion.

- To assess the overall safety and tolerability of this drug in these patients.

- To assess the overall quality of life of patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive oral rosiglitazone once daily for 7 weeks in the absence of disease
progression or unacceptable toxicity.

Blood, urine, and saliva samples are collected periodically for laboratory studies.
Inflammatory markers (C-reactive protein, interleukin-6 [IL-6], serum sialic acid, soluble
intracellular and vascular adhesion molecules [sICAM-1, and sVCAM-1], and amyloid A) are
measured at baseline and at the completion of study treatment; salivary cortisol and 24-hour
urinary-free cortisol levels are measured at baseline and weekly during study treatment;
dexamethasone suppression tests with serum cortisol and corticotrophin (CRH) stimulation
test are performed at baseline and at the completion of study treatment; prolactin,
insulin-like growth factor-1 (IGF1), thyroid function, and sex steroid hormones are measured
at baseline and at the completion of study treatment; and dynamic pituitary function testing
(arginine/growth hormone-releasing hormone [GHRH] testing to measure growth hormone
secretion) is performed at baseline.

Inclusion Criteria


- Clinically demonstrable ACTH-secreting pituitary tumor

- Pituitary tumor demonstrated on MRI with and without contrast AND/OR evidence of
a central ACTH source following inferior petrosal sinus sampling

- Newly diagnosed disease

- Biochemically active disease that is not adequately controlled, as demonstrated by
the following standard criteria:

- Elevated 24-hour urinary-free cortisol levels on at least 2 separate 24-hour
urine collections 1 week apart

- Lack of suppression of serum cortisol to < 1.8 μg/dL (at 8 am) following
administration of 1 mg of dexamethasone at 11 pm the night before

- Measurable plasma ACTH levels

- Patient is hypercortisolemic and does not wish to receive alternate steroid-lowering
therapy, such as ketoconazole and/or metyrapone

- Patients with evidence of optic nerve or chiasm compression on post-operative MRI
must have a normal visual field evaluation by Goldman perimetry

- No visual field abnormalities

- Hypopituitarism* allowed, as evidenced by any or all of the following:

- Subnormal growth hormone (GH) response to arginine/growth hormone-releasing
hormone (GHRH) testing (normal response is an increase of > 4 ng/mL)

- Low age-and sex-matched insulin-like growth factor-1 (IGF-1) levels

- Low thyroid-stimulating hormone (TSH) levels

- Low free triiodothyronine (T3) and free thyroxine (T4) levels

- Low estradiol levels

- Low luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in
postmenopausal female patients

- Low testosterone, LH, and FSH levels in male patients NOTE: *Patients who are
diagnosed with hypopituitarism will initiate thyroid hormone replacement therapy
prior to pituitary surgery as part of routine care. Other hormone replacement,
such as sex steroids or growth hormone, will not be initiated during the study.


- Not pregnant or nursing

- Fertile patients must use effective contraception (if oral contraception is used, it
must be used for ≥ 2 months prior to, during, and for 1 month after completion of
study therapy)

- No clinically significant renal, hematologic, or hepatic abnormalities

- No prior or concurrent medical condition that may interfere with the conduct of the
study or the evaluation of its results, in the opinion of the investigator or the
DSMB compliance officer

- No history of immunocompromise, including HIV positivity by ELISA and western blot

- No alcohol or drug abuse within the past 6 months

- No blood donation (≥ 400 mL) within the past 2 months

- No other active malignant disease within the past 5 years except for basal cell
carcinoma or carcinoma in situ of the cervix

- No active or suspected acute or chronic uncontrolled infection

- No severe osteoporosis, defined as bone mineral density T scores < 2.5 standard
deviations below age-matched controls

- No history of noncompliance to medical regimens

- Considered reliable

- Able to complete the entire study


- More than 3 months since prior rosiglitazone or other thiazolidinedione

- No prior or concurrent radiotherapy for pituitary tumor

- More than 1 month since prior participation in any clinical investigation involving
an investigational drug

- More than 30 days since prior unlicensed drugs

- No concurrent pituitary surgery

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Percentage of responders

Safety Issue:


Principal Investigator

Anthony Heaney, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Jonsson Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

April 2007

Completion Date:

Related Keywords:

  • Cushing's Disease
  • ACTH-producing pituitary tumor
  • Cushing Syndrome
  • Pituitary ACTH Hypersecretion
  • Pituitary Neoplasms



Jonsson Comprehensive Cancer Center at UCLALos Angeles, California  90095-1781