Study of Thyrotropin-Releasing Hormone in Normal Volunteers and in Patients With Thyroid or Pituitary Abnormalities

NCT00054756 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 03009803-DK-0098
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

Brief Summary

This study will determine the safety and activity of a new formulation of thyrotropin-releasing hormone (TRH), a drug used for diagnosing and evaluating patients with certain thyroid gland abnormalities. Normal thyroid gland function depends on proper chemical signaling between the thyroid gland, the hypothalamus (the part of the brain where TRH is made), and the pituitary (another part of the brain). The TRH test helps assess this interaction. Production of the only FDA-approved preparation of TRH was stopped in July 2002. As a result, to have a continuous source of TRH available for NIH clinical and research purposes, the NIH Clinical Center (CC) Pharmacy Department produced a pharmaceutical grade formulation of TRH for patient use. This study will test the CC formulation in healthy volunteers to show that its activity and side effects are similar to those of the previously available commercial test preparation. It will then be studied in CC patients for whom the diagnostic test is recommended. Healthy volunteers between 18 and 65 years of age and all patients requiring TRH evaluation of hypothalamic-pituitary-thyroid gland interaction may be eligible for this study. Patients include those with pituitary reserve, inconsistent thyroid function test, inappropriate TSH secretion, or pre- and post-operative evaluation of pituitary tumors. Normal volunteers will be screened with a medical history, physical examination, and blood tests. Women of child-bearing potential will be given a pregnancy test; pregnant and breast-feeding women may not participate. The TRH test procedure will be the same for healthy volunteers and patients. All participants fast from midnight before the morning of the test. In the morning, a catheter (flexible plastic tube) is inserted into an arm vein for easy injection of the TRH and collection of blood samples. Blood pressure is monitored before and during the test. A blood sample is drawn, and then TRH is given through the catheter over a 1-minute period. Another nine blood samples are collected over a 3-hour period from the time of the TRH injection for measuring levels of various hormones. A total of less than 4 tablespoons of blood is taken for the test.

Conditions

Healthy; Pituitary Disease; Thyroid Disease

Keywords

Hypothalamic Releasing Factor; Neuropeptide; Diagnostic Testing; Pituitary Tumors; Central Hypothyroidism; Pituitary Disorder; Thyroid Disorder; Healthy Volunteer

Outcome Measures

Primary Outcomes (1)

• TSH Response to TRH

  Serum TSH Levels in Response to TRH Administration

  180 minutes from infusion

Study Arms (1)

Thyrotropin Releasing Hormone

EXPERIMENTAL

Subjects receiving TRH (Thyrotropin Releasing Hormone)

Drug: TRH (Thyrotropin Releasing Hormone)

Interventions

TRH (Thyrotropin Releasing Hormone) DRUG

Thyrotropin Releasing Hormone

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• All adults and children requiring dynamic testing of the hypothalamic-pituitary axis for the evaluation of pituitary reserve, inconsistent thyroid function test, inappropriate TSH secretion, or pre-and post-operative evaluation of pituitary adenomas (glycoprotein hormone secreting tumors, growth hormone secreting tumors and TSH secreting tumors).

You may not qualify if:

• Uncontrolled hypertension;
• Uncontrolled seizure disorder;
• Unstable coronary disease;
• Known allergy to TRH.
• RESEARCH PROTOCOLS
• TRH is available for use in other IRB approved research protocols either using the standard diagnostic testing protocol or the modified TRH test.
• Untreated hypertension;
• Coronary artery disease;
• History of asthma;
• History of seizures;
• Pregnancy;
• Known allergy to TRH.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Jackson IM. Thyrotropin-releasing hormone. N Engl J Med. 1982 Jan 21;306(3):145-55. doi: 10.1056/NEJM198201213060305. No abstract available.

  PMID: 6798440 BACKGROUND

• Haigler ED Jr, Pittman JA Jr, Hershman JM, Baugh CM. Direct evaluation of pituitary thyrotopin reserve utilizing synthetic thyrotopin releasing hormone. J Clin Endocrinol Metab. 1971 Oct;33(4):573-81. doi: 10.1210/jcem-33-4-573. No abstract available.

  PMID: 4999252 BACKGROUND

• Faglia G. The clinical impact of the thyrotropin-releasing hormone test. Thyroid. 1998 Oct;8(10):903-8. doi: 10.1089/thy.1998.8.903.

  PMID: 9827657 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Pituitary Diseases; Thyroid Diseases; Pituitary Neoplasms; Hypothyroidism

Interventions

Thyrotropin-Releasing Hormone

Condition Hierarchy (Ancestors)

Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms

Intervention Hierarchy (Ancestors)

Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Limitations and Caveats

This study was conducted under an IND because the TRH was produced at NIH after the FDA approved manufacturer stopped producing the product. The intent of the study was to provide TRH for diagnostic purposes for patients at the NIH.

Results Point of Contact

• Title: Dr Joanna Klubo-Gwiezdzinska
• Organization: NIDDK

joanna.klubo-gwiezdzinska@nih.gov

301-496-1211

Study Officials

• Joanna Klubo-Gwiezdzinska, M.D.

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2003
• First Posted: February 10, 2003
• Study Start: February 7, 2003
• Primary Completion: September 26, 2014
• Study Completion: September 26, 2014
• Last Updated: August 8, 2018
• Results First Posted: August 8, 2018

Record last verified: 2018-04

Locations

US (1)