Study of Adrenalectomy Versus Observation for Subclinical Hypercortisolism

NCT02001051 | Terminated Phase 2 Results

• 2 other identifiers: 14002114-C-0021
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Adrenal tumors are a common kind of tumor. Some of these secrete extra cortisol into the body, which can lead to diabetes, obesity, and other diseases. Some people with extra cortisol will show symptoms like bruising and muscle weakness. Others will show no signs. This is called subclinical hypercortisolism. Some of these adrenal tumors become malignant. Researchers want to know the best way to treat people with subclinical hypercortisolism. They want to know if removing the tumor by surgery reduces the long-term effects of the disease. Objectives: \- To see if removing an adrenal tumor by surgery improves blood pressure, diabetes, obesity, osteoporosis, or cholesterol, and cancer detection. Eligibility: \- Adults 18 and older with an adrenal tumor and high cortisol levels. Design:

• Participants will be screened with medical history, blood tests, and a computed tomography (CT) scan.
• Participants will have a baseline visit. They will have blood and urine tests and 7 scans. For most scans, a substance is injected through a tube in the arm. Participants will lie still on a table in a machine that takes images.
• Participants will have surgery to remove their tumor. Some will have surgery right away. Some will have surgery 6 months later, after 2 follow-up appointments.
• Participants will have 4 follow-up visits in the first year after surgery. They will have 2 visits the second year, then yearly visits for 3 years. At each follow-up visit, they will have scans and blood tests.

Conditions

Subclinical Hypercortisolism; Cushing Syndrome; Adrenal Neoplasm

Keywords

Diabetes, Hypertension, Hypercholesterolemia, Obesity, and Osteoporosis.; Nonoperative and Operative Management; Adrenal Incidentalomas; Excess of Cortisol

Outcome Measures

Primary Outcomes (2)

• Proportion of Patients That Have Normalization and/or Improvement of Metabolic Complications After Adrenalectomy

  Normalization and/or improvement of metabolic complications including hypertension, diabetes, osteoporosis, hypercholesterolemia and/or obesity after adrenalectomy is defined as 35% of patients who improve with surgery versus 5% who do not have surgery.

  Assessed at 6 months

• Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)

  Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

  Date treatment consent signed to date off study, approximately 39 months and 27 days

Secondary Outcomes (6)

• Proportion of Patients Who Are Found to Have Adrenal Cancer After Adrenalectomy

  Assessed at 6 months

• Proportion of Patients Who Were Diagnosed With Subclinical Hypercortisolism by Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)/Computed Tomography (CT) Scan

  Assessed at 6 months

• To Determine the Optimal Diagnostic Test for Subclinical Hypercortisolism

  Assessed at 6 months

• Proportion of Patients That Have Improvement in Quality of Life (QOL) After Adrenalectomy Compared to Medical Therapy

  Assessed at 6 months

• Proportion of Patients That Developed Deep Venous Thrombosis With Subclinical Hypercortisolism

  Assessed at 6 months

Study Arms (2)

Operative Arm

OTHER

operative arm

Procedure: Adrenalectomy

Delayed Operative Arm

OTHER

delayed operative arm

Other: Observation

Interventions

Adrenalectomy PROCEDURE

Surgery to remove tumor when enrolled in the protocol.

Operative Arm

Observation OTHER

Observation for 6 months prior to surgery

Delayed Operative Arm

Eligibility Criteria

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

You may qualify if:

• An individual with an adrenal neoplasm less than 5 cm in size with biochemically confirmed evidence of hypercortisolism (2 out of 3: dexamethasone suppression test (DST) \>3 mcgl/dL, elevated urine free cortisol, and/or morning adrenocorticotropic hormone (ACTH) \<2.2 pmol/l) without overt clinical signs and symptoms.
• Age greater than or equal to 18 years.
• Adults must be able to understand and sign the informed consent document.
• Patients must have laboratory and physical examination parameters within acceptable limits by standard of practice.

You may not qualify if:

• Biochemically and/or radiologically confirmed pheochromocytoma, hyperaldosteronism, or adrenocortical carcinoma.
• Nonfunctioning adrenal neoplasm.
• Pre-existing cancers and/or metastatic disease to the adrenal glands.
• Pregnancy and/or lactation.
• Lack of metabolic complications.
• Imaging features worrisome for malignancy (heterogeneous tumor, presence of calcifications, necrosis, \>10 Hounsfield units on an unenhanced computed tomography (CT) scan, and delayed washout of contrast).

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• Clinical Center Office of the Associates Director for Radiologic&Imaging Sciences: collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Toniato A, Merante-Boschin I, Opocher G, Pelizzo MR, Schiavi F, Ballotta E. Surgical versus conservative management for subclinical Cushing syndrome in adrenal incidentalomas: a prospective randomized study. Ann Surg. 2009 Mar;249(3):388-91. doi: 10.1097/SLA.0b013e31819a47d2.

  PMID: 19247023 BACKGROUND

• Reincke M. Subclinical Cushing's syndrome. Endocrinol Metab Clin North Am. 2000 Mar;29(1):43-56. doi: 10.1016/s0889-8529(05)70115-8.

  PMID: 10732263 BACKGROUND

• Chiodini I. Clinical review: Diagnosis and treatment of subclinical hypercortisolism. J Clin Endocrinol Metab. 2011 May;96(5):1223-36. doi: 10.1210/jc.2010-2722. Epub 2011 Mar 2.

  PMID: 21367932 BACKGROUND

• Neychev V, Steinberg SM, Yang L, Mehta A, Nilubol N, Keil MF, Nieman L, Stratakis CA, Kebebew E. Long-Term Outcome of Bilateral Laparoscopic Adrenalectomy Measured by Disease-Specific Questionnaire in a Unique Group of Patients with Cushing's Syndrome. Ann Surg Oncol. 2015 Dec;22 Suppl 3(Suppl 3):S699-706. doi: 10.1245/s10434-015-4605-1. Epub 2015 May 13.

  PMID: 25968622 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Cushing Syndrome; Adrenal Gland Neoplasms; Diabetes Mellitus; Hypertension; Hypercholesterolemia; Obesity; Osteoporosis; Adrenal incidentaloma

Interventions

Adrenalectomy; Observation

Condition Hierarchy (Ancestors)

Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Vascular Diseases; Cardiovascular Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Endocrine Surgical Procedures; Surgical Procedures, Operative; Methods; Investigative Techniques

Results Point of Contact

• Title: Dr. Dhaval Patel
• Organization: National Cancer Institute

pateldt@nih.gov

301-827-4989

Study Officials

• Dhaval T Patel, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 27, 2013
• First Posted: December 4, 2013
• Study Start: November 27, 2013
• Primary Completion: August 22, 2017
• Study Completion: February 26, 2018
• Last Updated: June 14, 2018
• Results First Posted: May 8, 2018

Record last verified: 2018-05

Locations

US (1)