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Circulating miRNA in Primary Hyperparathyroidism

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ClinicalTrials.gov Identifier: NCT03931109
Recruitment Status : Recruiting
First Posted : April 30, 2019
Last Update Posted : April 30, 2019
Sponsor:
Information provided by (Responsible Party):
University of Pennsylvania

Brief Summary:
The goal of this study is to: 1. Analyze the expression levels of circulating (serum) miRNAs in primary hyperparathyroidism patients with and without osteoporosis, and patients with osteoporosis undergoing thyroidectomy, and to correlate with clinical markers of bone remodeling including biochemical and radiologic studies. 2. To evaluate serum miRNA levels after treatment with parathyroidectomy.

Condition or disease
Primary Hyperparathyroidism Osteoporosis, Postmenopausal

Detailed Description:

Osteoporosis and osteopenia are chronic diseases disproportionately affecting the elderly. In the United States, the prevalence of osteoporosis is projected to increase from 10 million in 2005 to 14 million in 2025, due to population aging. Similarly, the economic cost of osteoporotic fractures is projected to increase to $25 billion by 2025. Primary hyperparathyroidism (PHPT) is one of the few reversible causes of osteoporosis and fragility fractures. PHPT is the third most common endocrine disorder, with an incidence of 27-30 per 100,000 person-years, and increasing with age; half of all patients with PHPT are post-menopausal women, a population at high risk for osteoporosis at baseline. All forms of PHPT are characterized by loss of the normal negative feedback relationship between serum calcium and parathyroid hormone (PTH) secretion, leading to hypercalcemia and hyperparathyroidism. Classic PHPT is characterized by skeletal, renal, gastrointestinal and neuropsychiatric manifestations. Skeletal manifestations of classic PHPT are mediated by osteoblast inhibition and osteoclast stimulation, leading to increased bone remodeling. The catabolic effects of chronic PTH excess may present as osteitis fibrosa cystica, brown tumors, pathologic fractures, bone pain, osteoporosis or osteopenia. Although frank osteitis fibrosa cystica is an increasingly rare presentation of PHPT in the United States, affecting 2% of patients, osteoporosis is reported in 39-63% of patients, with preferential loss of bone density in cortical sites. Fragility fractures are significantly associated with PHPT, particularly in postmenopausal women. Both decreases in bone mineral density (BMD) and fragility fractures are considered indications for parathyroidectomy in patients with asymptomatic PHPT. Parathyroidectomy has been demonstrated to improve BMD in prospective studies of PHPT patients with osteoporosis; some studies suggest that more benefit may be seen in pre-menopausal women. Current research in bone remodeling has identified microRNAs (miRNAs), novel biomarkers with both diagnostic and therapeutic potential. miRNAs are short, single stranded, non-coding RNAs which regulate posttranscriptional expression of mRNA. miRNAs have been extensively implicated in bone remodeling and homeostasis. Circulating miRNAs have been shown to correlate with fragility fractures, and are conserved across subpopulations of osteoporotic patients. miRNA panels have been suggested to have the potential to assist in diagnosis, prognosis, and are promising targets for directed therapy. Although miRNAs have been investigated in conjunction with pre-menopausal, postmenopausal, idiopathic and diabetic osteoporosis, no research to date has explored the miRNA profile of PHPT patients with osteoporosis. Similarly, although in vitro experiments have demonstrated miRNA response to bisphosphonates, no clear correlation has been established between therapeutic interventions and miRNA levels in vivo. The goal of this study is therefore two-fold; first, to analyze the expression levels of circulating miRNAs in PHPT patients with and without osteoporosis; and second, to evaluate miRNA levels after treatment with parathyroidectomy.

This is a prospective, non-randomized pilot study. Post-menopausal female subjects with and without osteoporosis, undergoing neck surgery or non-operative management will be recruited. Informed consent will be obtained. Venipuncture will be performed and serum and plasma isolated from study subjects. Analysis of serum miRNA and biochemical and clinical markers of bone remodeling will be performed. Clinical care will proceed as planned. Subjects undergoing surgery will be reassessed one year after operative intervention for miRNA and clinical and biochemical markers.


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Study Type : Observational [Patient Registry]
Estimated Enrollment : 100 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 1 Year
Official Title: Circulating microRNA Signatures in Primary Hyperparathyroidism
Actual Study Start Date : September 7, 2018
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : September 2021


Group/Cohort
PHPT w/ Osteoporosis
Primary hyperparathyroidism patients with osteoporosis undergoing parathyroidectomy
PHPT w/o Osteoporosis
Primary hyperparathyroidism patients without osteoporosis undergoing parathyroidectomy
Thyroid w/ Osteoporosis
Thyroid disease patients with osteoporosis undergoing thyroidectomy



Primary Outcome Measures :
  1. circulating microRNAs in primary hyperparathyroidism patients [ Time Frame: 2019-2021 ]
    Serum miRNA levels

  2. serum miRNA after parathyroidectomy [ Time Frame: 2019-2021 ]
    clinical markers of bone remodeling, including serum levels of bone-specific alkaline phosphatase, osteocalcin, P1NP, CTX, calcium, phosphate, Vitamin D metabolites, and PTH; urine calcium; and DXA scan


Biospecimen Retention:   Samples With DNA
Blood Samples


Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
post-menopausal women diagnosed with primary hyperparathyroidism.
Criteria

Inclusion Criteria:

  • post menopausal
  • has had DXA scan
  • has 24 hr Urine Calcium
  • Elevated serum calcium
  • Vitamin D above 20 ng/ml
  • capable of giving informed consent
  • female
  • indication for biochemical primary hyperparathyroidism or an indication for partial or total thyroidectomy

Exclusion Criteria:

  • history of ESRD on dialysis or renal osteodystrophy
  • prior parathyroidectomy
  • hyper or hypothyroid by TSH
  • currently taking steroids or has been on steroids for more than 7 days in the last two years
  • estrogen therapy within the last two years
  • bisphosphonate therapy within the last two years
  • diagnosis of Cushing's disease or Cushing's syndrome
  • taking biotin within 24 hours of blood draw

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03931109


Contacts
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Contact: Jae P Ermer, BS 2156151605 jae.ermer@pennmedicine.upenn.edu
Contact: Heather Wachtel, MD 2156153346 heather.wachtel@pennmedicine.upenn.edu

Locations
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United States, Pennsylvania
Perelman Center for Advanced Medicine/ Hospital of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Jae Ermer    215-615-1605    jae.ermer@pennmedicine.upenn.edu   
Principal Investigator: Heather Wachtel, MD         
Sponsors and Collaborators
University of Pennsylvania
Investigators
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Principal Investigator: Heather Wachtel, MD University of Pennsylvania Health System
  Study Documents (Full-Text)

Documents provided by University of Pennsylvania:
Informed Consent Form  [PDF] February 6, 2018


Publications:

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Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT03931109     History of Changes
Other Study ID Numbers: 829615
First Posted: April 30, 2019    Key Record Dates
Last Update Posted: April 30, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Pennsylvania:
Osteoporosis
primary hyperparathyroidism
miRNA
Bone remodeling
parathyroidectomy
Osteopenia
postmenopausal
Additional relevant MeSH terms:
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Osteoporosis
Osteoporosis, Postmenopausal
Hyperparathyroidism
Hyperparathyroidism, Primary
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Metabolic Diseases
Parathyroid Diseases
Endocrine System Diseases