Studies of Elevated Parathyroid Activity

• ClinicalTrials.gov Identifier: NCT00001277
• Recruitment Status: Completed
• First Posted: November 4, 1999
• Last Update Posted: December 28, 2020
• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) )

Study Description

Brief Summary:

Patients whose parathyroid activity is elevated above normal are referred to as having hyperparathyroidism. This study will help researchers better understand the causes of hyperthyroidism and to evaluate and improve methods for diagnosis and treatment.

In this study, patients diagnosed with or suspected of having hyperparathyroidism will be selected to participate. In addition, patients with related conditions such as parathyroid tumors, will also be selected.

Subjects will be asked to provide blood and urine for testing to confirm their condition. They will then be surgically treated by removal of the parathyroid gland(s) (parathyroidectomy).

Subjects with parathyroid tumors will undergo several diagnostic tests to determine the exact location of the tumor as well as the tumor's activity. The tests may include; ultrasounds, nuclear scanning, CT scans, MRI, and specialized blood testing.

Sometimes parathyroidectomy leads to hypoparathyroidism. Options for treating the patients after the surgical procedure will also be addressed. Calcium and Vitamin D supplements are typically the mainstay of post parathyroidectomy therapy. Other potential treatments include transplanting the parathyroid gland(s) to other areas of the body.

Condition or disease	Intervention/treatment	Phase
Hyperparathyroidism; Hypocalcemia; Parathyroid Neoplasm; Multiple Endocrine Neoplasia; MEN1	Drug: 68Ga-Dotatate; Drug: 18F-DOPA	Not Applicable

Detailed Description:

Patients with confirmed or suspected primary hyperparathyroidism or complications therefrom (such as postoperative hypoparathyroidism) will be admitted for diagnosis and treatment. The principal diagnostic components are calcium in serum and urine, parathyroid hormone in serum, and mutation tests on germline or tumor DNA. Patients with moderately to severe primary hyperparathyroidism will be treated. Treatment will be mainly by parathyroidectomy. Preoperative testing to localize parathyroid neoplasm(s) will be used usually and with more extended methods in cases with prior neck surgery. Other options are medications or no intervention. Patients with a hyperparathyroid syndrome may be managed for their extraparathyroid features (medical management or surgical treatment). Preoperative tumor localization tests will be selected according to clinical indications from the following: ultrasound, technetium-thallium scan, computerized tomography, magnetic resonance imaging, somatostatin receptor imaging, fine needle aspiration for parathyroid hormone assay, selective arteriogram, selective venous catheterization for parathyroid hormone assay. Options for management of postoperative hypocalcemia include calcium, vitamin D analogs, parathyroid autografts and synthetic parathyroid hormone. Research specimens may consist of blood or tumors. In addition, a substudy for patients with multiple endocrine neoplasia type 1 (MEN1) will assess the utility of two PET/CT scans with radiotracers (68Gallium-DOTATATE and 18F-DOPA).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1553 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Studies of Hyperparathyroidism and Related Disorders
• Actual Study Start Date: December 15, 1993
• Actual Primary Completion Date: December 23, 2020
• Actual Study Completion Date: December 23, 2020

Arms and Interventions

Arm

Intervention/treatment

Experimental: Main; Patients with confirmed or suspected primary hyperparathyroidism or complications therefrom (such as postoperative hypoparathyroidism) will be admitted for diagnosis and treatment.

Drug: 68Ga-Dotatate; -To compare the efficacy of 68Ga- Dotatate PET/CT scan versus 18FDOPA PET/CT, MRI and CT scan in detecting known and occult primary and metastatic bronchial, gastrointestinal and pancreatic neuroendocrine tumors -To evaluate 68Gallium-Dotatate versus 18F-DOPA PET /CT uptake in NETs and its association with tumor differentiation. (2)To determine whether 68Gallium- Dotatate and/or 18FDOPA PET/CT uptake value is predictive of tumor growth and/or disease progression and of its differentiation state.; Drug: 18F-DOPA; -To compare the efficacy of 68Ga- Dotatate PET/CT scan versus 18FDOPA PET/CT, MRI and CT scan in detecting known and occult primary and metastatic bronchial, gastrointestinal and pancreatic neuroendocrine tumors -To evaluate 68Gallium-Dotatate versus 18F-DOPA PET /CT uptake in NETs and its association with tumor differentiation -To determine whether 68Gallium-Dotatate and/or 18FDOPA PET/CT uptake value is predictive of tumor growth and/or disease progression and of its differentiation state.

Outcome Measures

Primary Outcome Measures :

1. Evaluate natural history of hyperparathyroidism [ Time Frame: Yearly ]
   The purpose of this study is to understand the causes of primary hyperparathyroidism, to evaluate and improve methods for diagnosis and treatment, and to provide insight into the mechanisms of normal parathyroid function. Hereditary causes of primary hyperparathyroidism will be characterized. Methods of pre-operative parathyroid gland localization will be evaluated (6, 7, 8). Genes that contribute to development of parathyroid tumors will be analyzed (4, 9, 10).

Secondary Outcome Measures :

1. To compare the efficacy of 68Ga-Dotatate PET/CT scan versus 18F-DOPA PET/CT, MRI and CT scan [ Time Frame: Yearly ]
   To compare the efficacy of 68Ga-Dotatate PET/CT scan versus 18F-DOPA PET/CT, MRI and CT scan in detecting known and occult primary and metastatic bronchial, gastrointestinal and pancreatic neuroendocrine tumors in yearly intervals as per standard of care.
2. To evaluate 68Gallium-Dotatate versus 18F-DOPA PET/CT uptake in NETs and its association with tumor differentiation [ Time Frame: Yearly ]
   There is the potential for direct benefit for patients participating in this study if the study results show 18FDOPA PET/CT imaging to be more accurate than the current standard 68Gallium- DOTATATE at detecting primary lesions or metastasis. The future application of 18F-DOPA imaging modality in other patients could lead to early detection of solid gastrointestinal or pancreatic lesions and metastatic lesions, which would improve early management of these lesions and potentially have an impact on the overall course of the disease.
3. To determine whether 68Gallium-Dotatate and/or 18F-DOPA PET/CT uptake value is predictive of tumor growth and/or disease progression and of its differentiation state [ Time Frame: Yearly ]
   There is the potential for direct benefit for patients participating in this study if the study results show 18FDOPA PET/CT imaging to be more accurate than the current standard 68Gallium- DOTATATE at detecting primary lesions or metastasis. The future application of 18F-DOPA imaging modality in other patients could lead to early detection of solid gastrointestinal or pancreatic lesions and metastatic lesions, which would improve early management of these lesions and potentially have an impact on the overall course of the disease.

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

• INCLUSION CRITERIA:
• Patients who have genetically confirmed MEN1 or clinical criteria of MEN1.
• Age greater than age 18.
• For females: Negative urine pregnancy test OR post-menopausal for at least 2 years OR patient has had a hysterectomy

EXCLUSION CRITERIA:

• Serious underlying medical conditions that restrict diagnostic testing or therapy such as renal failure or congestive cardiac failure
• Patients unable or unwilling to give informed consent
• Pregnant or lactating women: Pregnant women are excluded from this study because the effects of 68Ga-DOTATATE in pregnancy are not known. Because there is an unknown but potential risk for adverse events in nursing infants secondary to administration of 68Ga-DOTATATE in the mother, women who are breastfeeding are also excluded from this study
• Patients that have recognized concurrent active infection
• Patients with known hypersensitivity to carbidopa, or who are concurrently taking a nonselective monoamine oxidase (MAO) inhibitor..

Contacts and Locations

Locations

United States, Maryland

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Jenny E Blau, M.D.; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page 

• Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• ClinicalTrials.gov Identifier: NCT00001277
• Other Study ID Numbers: 910085; 91-DK-0085
• First Posted: November 4, 1999
• Last Update Posted: December 28, 2020
• Last Verified: December 23, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) ):

Hypoglycemia; Genetics; Hyperparathyroidism

Additional relevant MeSH terms:

Endocrine Gland Neoplasms; Multiple Endocrine Neoplasia; Parathyroid Neoplasms; Hypocalcemia; Hyperparathyroidism; Neoplasms; Parathyroid Diseases; Endocrine System Diseases; Calcium Metabolism Disorders; Metabolic Diseases; Water-Electrolyte Imbalance; Neoplasms by Site; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Head and Neck Neoplasms