Studies of Elevated Parathyroid Activity

• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00001277
• Collaborator: (none)
• Enrollment: 1,553
• Location: 1
• Arms: 2
• Actual Duration (Months): 324.3
• Patients Per Site Per Month: 4.8

Study Details

Study Description

Brief Summary

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

Clinical Trial: An imaging substudy was added to this protocol in 2018. Patients with multiple endocrine neoplasia type 1 (MEN1) will have 68Gallium-Dotatate Positron Emission Tomography (PET) - Computed Tomography (CT), 18F-DOPA PET/CT, MRI, and CT scans and the number of lesions detected by each of these types of scans will be compared.

Condition or Disease	Intervention/Treatment	Phase
Hyperparathyroidism; Hypercalcemia; Parathyroid Neoplasm; Multiple Endocrine Neoplasia; MEN1	Drug: 68Ga-Dotatate; Drug: 18F-DOPA	Phase 2

Detailed Description

Observational: 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 moderate to severe primary hyperparathyroidism will be treated. Treatment will be mainly by parathyroidectomy. Other options are medications or no intervention. Patients with a hyperparathyroid syndrome may be managed for their extraparathyroid features. Preoperative testing to localize parathyroid neoplasm(s) will be used usually and with more extended methods in cases with prior neck surgery. Preoperative tumor localization tests will be selected according to clinical indications from the following: ultrasound, technetium-thallium scan, computerized tomography, magnetic resonance 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.

Clinical Trial: An imaging substudy was added to this protocol in 2018. Patients with MEN1 will have 68Ga-Dotatate PET/CT, 18F-DOPA PET/CT, MRI, and CT scans and the number of lesions detected by each of these types of scans will be compared.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1553 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Studies of Hyperparathyroidism and Related Disorders
• Actual Study Start Date: Dec 15, 1993
• Actual Primary Completion Date: Mar 11, 2020
• Actual Study Completion Date: Dec 23, 2020

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Primary hyperparathyroidism Patients with confirmed or suspected primary hyperparathyroidism or complications
Experimental: DOTATATE and F-DOPA Patients scanned using imaging agents 68GALLIUM-DOTATATE and 18F-DOPA	Drug: 68Ga-Dotatate; 68Ga-Dotatate PET/CT will be administered prior to a PET/CT scan to detect known and occult primary and metastatic bronchial, gastrointestinal and pancreatic neuroendocrine tumors.; Drug: 18F-DOPA; 18F-DOPA PET/CT will be administered prior to a whole-body scan to detect known and occult primary and metastatic bronchial, gastrointestinal and pancreatic neuroendocrine tumors.

Outcome Measures

Primary Outcome Measures

1. Type of Hyperparathyroidism [First year]

   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. Patients were categorized as follows: MEN1: Diagnosed by demonstration of a germline variant in MEN1 gene or one of the following: a) two of three primary MEN1 manifestations b) one primary MEN1 manifestation with a family member with MEN1. Other familial: Non-MEN1 patients who had a positive family history of hyperparathyroidism suspicious for underlying germline predisposition syndrome. Sporadic: Patients who did not have a positive family history of hyperparathyroidism. Unknown: No data to help categorize the patients in any of the above categories.

2. Organs With Identified Lesions [Days 1-6]

   For each organ, agreement between 68Ga-DOTATATE and 18F-DOPA

3. Number of Lesions Identified [Days 1-6]

   The total number of lesions identified by each imaging modality

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Months and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

INCLUSION CRITERIA:

• Patients who have genetically confirmed MEN1 or clinical criteria of MEN1.

• 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

	Site	City	State	Country	Postal Code
1	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: Smita Jha, M.D., National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 17, 2020

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

Publications

None provided.

• 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: Nov 4, 1999
• Last Update Posted: Jun 7, 2022
• Last Verified: Feb 7, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by 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; Hypercalcemia; Hyperparathyroidism

Study Results

Participant Flow

Arm/Group Title	Primary Hyperparathyroidism - Incomplete Data	Primary Hyperparathyroidism	DOTATATE and F-DOPA
Arm/Group Description	Patients with confirmed or suspected primary hyperparathyroidism or complications who are missing age and other baseline data because of changes in data management system	Patients with confirmed or suspected primary hyperparathyroidism or complications	Patients scanned using imaging agents 68GALLIUM-DOTATATE and 18F-DOPA 68Ga-Dotatate: 68Ga-Dotatate PET/CT will be administered prior to a PET/CT scan to detect known and occult primary and metastatic bronchial, gastrointestinal and pancreatic neuroendocrine tumors. 18F-DOPA: 18F-DOPA PET/CT will be administered prior to a whole-body scan to detect known and occult primary and metastatic bronchial, gastrointestinal and pancreatic neuroendocrine tumors.
Period Title: Overall Study
STARTED	634	900	19
COMPLETED	634	900	16
NOT COMPLETED	0	0	3

Baseline Characteristics

Arm/Group Title	Primary Hyperparathyroidism - Incomplete Data	Primary Hyperparathyroidism	DOTATATE and F-DOPA	Total
Arm/Group Description	Patients with confirmed or suspected primary hyperparathyroidism or complications who are missing age and other baseline data because of changes in data management system	Patients with confirmed or suspected primary hyperparathyroidism or complications	Patients scanned using imaging agents 68GALLIUM-DOTATATE and 18F-DOPA 68Ga-Dotatate: 68Ga-Dotatate PET/CT will be administered prior to a PET/CT scan to detect known and occult primary and metastatic bronchial, gastrointestinal and pancreatic neuroendocrine tumors. 18F-DOPA: 18F-DOPA PET/CT will be administered prior to a whole-body scan to detect known and occult primary and metastatic bronchial, gastrointestinal and pancreatic neuroendocrine tumors.	Total of all reporting groups
Overall Participants	634	900	19	1553
Age (Years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [Years]	48	54	48
Sex: Female, Male (Count of Participants)
Female	409 64.5%	582 64.7%	6 31.6%	997 64.2%
Male	225 35.5%	318 35.3%	13 68.4%	556 35.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	1 5.3%	1 0.1%
Not Hispanic or Latino	0 0%	0 0%	14 73.7%	14 0.9%
Unknown or Not Reported	634 100%	900 100%	4 21.1%	1538 99%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	4 0.4%	0 0%	4 0.3%
Asian	0 0%	25 2.8%	0 0%	25 1.6%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.1%	0 0%	1 0.1%
Black or African American	0 0%	100 11.1%	1 5.3%	101 6.5%
White	0 0%	719 79.9%	16 84.2%	735 47.3%
More than one race	0 0%	13 1.4%	0 0%	13 0.8%
Unknown or Not Reported	634 100%	38 4.2%	2 10.5%	674 43.4%
Region of Enrollment (participants) [Number]
United States	634 100%	900 100%	19 100%	1553 100%

Outcome Measures

1. Primary Outcome

Title	Type of Hyperparathyroidism
Description	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. Patients were categorized as follows: MEN1: Diagnosed by demonstration of a germline variant in MEN1 gene or one of the following: a) two of three primary MEN1 manifestations b) one primary MEN1 manifestation with a family member with MEN1. Other familial: Non-MEN1 patients who had a positive family history of hyperparathyroidism suspicious for underlying germline predisposition syndrome. Sporadic: Patients who did not have a positive family history of hyperparathyroidism. Unknown: No data to help categorize the patients in any of the above categories.
Time Frame	First year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Primary Hyperparathyroidism - Incomplete Data	Primary Hyperparathyroidism	DOTATATE and F-DOPA
Arm/Group Description	Patients with confirmed or suspected primary hyperparathyroidism or complications who are missing age and other baseline data because of changes in data management system	Patients with confirmed or suspected primary hyperparathyroidism or complications	Patients scanned using imaging agents 68GALLIUM-DOTATATE and 18F-DOPA 68Ga-Dotatate: 68Ga-Dotatate PET/CT will be administered prior to a PET/CT scan to detect known and occult primary and metastatic bronchial, gastrointestinal and pancreatic neuroendocrine tumors. 18F-DOPA: 18F-DOPA PET/CT will be administered prior to a whole-body scan to detect known and occult primary and metastatic bronchial, gastrointestinal and pancreatic neuroendocrine tumors.
Measure Participants	634	900	19
MEN1	90 14.2%	276 30.7%	19 100%
Other familial	61 9.6%	116 12.9%	0 0%
Sporadic	456 71.9%	419 46.6%	0 0%
Unknown - insufficient information	27 4.3%	89 9.9%	0 0%

2. Primary Outcome

Title	Organs With Identified Lesions
Description	For each organ, agreement between 68Ga-DOTATATE and 18F-DOPA
Time Frame	Days 1-6

Outcome Measure Data

Analysis Population Description

Imaging was only conducted in the "DOTATATE and F-DOPA" Arm/Group and therefore results are only reported for this arm

Arm/Group Title	DOTATATE and F-DOPA
Arm/Group Description	Patients who received both DOTATATE and F-DOPA scans
Measure Participants	16
No lesions by Dotatate or F-DOPA	1 0.2%
Lesions by F-DOPA only	0 0%
Lesions by Dotatate only	7 1.1%
Lesions by Both	8 1.3%
No lesions by Dotatate or F-DOPA	13 2.1%
Lesions by F-DOPA only	0 0%
Lesions by Dotatate only	0 0%
Lesions by Both	3 0.5%
No lesions by Dotatate or F-DOPA	12 1.9%
Lesions by F-DOPA only	0 0%
Lesions by Dotatate only	3 0.5%
Lesions by Both	1 0.2%
No lesions by Dotatate or F-DOPA	3 0.5%
Lesions by F-DOPA only	0 0%
Lesions by Dotatate only	9 1.4%
Lesions by Both	4 0.6%
No lesions by Dotatate or F-DOPA	9 1.4%
Lesions by F-DOPA only	0 0%
Lesions by Dotatate only	6 0.9%
Lesions by Both	1 0.2%
No lesions by Dotatate or F-DOPA	11 1.7%
Lesions by F-DOPA only	0 0%
Lesions by Dotatate only	3 0.5%
Lesions by Both	2 0.3%
No lesions by Dotatate or F-DOPA	12 1.9%
Lesions by F-DOPA only	1 0.2%
Lesions by Dotatate only	3 0.5%
Lesions by Both	0 0%
No lesions by Dotatate or F-DOPA	7 1.1%
Lesions by F-DOPA only	0 0%
Lesions by Dotatate only	4 0.6%
Lesions by Both	5 0.8%

3. Primary Outcome

Title	Number of Lesions Identified
Description	The total number of lesions identified by each imaging modality
Time Frame	Days 1-6

Outcome Measure Data

Analysis Population Description

Imaging was only conducted in the "DOTATATE and F-DOPA" Arm/Group and therefore results are only reported for this arm. This outcome is only reported for the 16 patients who had both scans

Arm/Group Title	DOTATATE and F-DOPA
Arm/Group Description	Patients who received both DOTATATE and F-DOPA scans
Measure Participants	16
Measure Lesions	134
No lesions by Dotatate or F-DOPA	44
Lesions by F-DOPA only	1
Lesions by Dotatate only	67
Lesions by Both	22

Adverse Events

Time Frame	3 months
Arm/Group Title	Primary Hyperparathyroidism - Incomplete Data		Primary Hyperparathyroidism		DOTATATE and F-DOPA
Arm/Group Description	Patients with confirmed or suspected primary hyperparathyroidism or complications who are missing age and other baseline data because of changes in data management system		Patients with confirmed or suspected primary hyperparathyroidism or complications		Patients scanned using imaging agents 68GALLIUM-DOTATATE and 18F-DOPA 68Ga-Dotatate: 68Ga-Dotatate PET/CT will be administered prior to a PET/CT scan to detect known and occult primary and metastatic bronchial, gastrointestinal and pancreatic neuroendocrine tumors. 18F-DOPA: 18F-DOPA PET/CT will be administered prior to a whole-body scan to detect known and occult primary and metastatic bronchial, gastrointestinal and pancreatic neuroendocrine tumors.
All Cause Mortality
	Primary Hyperparathyroidism - Incomplete Data		Primary Hyperparathyroidism		DOTATATE and F-DOPA
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/634 (0%)		0/900 (0%)		0/19 (0%)
Serious Adverse Events
	Primary Hyperparathyroidism - Incomplete Data		Primary Hyperparathyroidism		DOTATATE and F-DOPA
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/634 (0%)		0/900 (0%)		0/19 (0%)
Other (Not Including Serious) Adverse Events
	Primary Hyperparathyroidism - Incomplete Data		Primary Hyperparathyroidism		DOTATATE and F-DOPA
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/634 (0%)		0/900 (0%)		1/19 (5.3%)
Gastrointestinal disorders
Abdominal pain	/634 (NaN)		0/900 (0%)		1/19 (5.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.