Circulating miRNA in Primary Hyperparathyroidism

Sponsor

University of Pennsylvania (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03931109

Collaborator

(none)

100

Enrollment

Location

46.8

Anticipated Duration (Months)

2.1

Patients Per Site Per Month

Study Details

Study Description

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	Intervention/Treatment	Phase
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.

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

100 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Circulating microRNA Signatures in Primary Hyperparathyroidism

Actual Study Start Date :

Sep 7, 2018

Anticipated Primary Completion Date :

Aug 1, 2022

Anticipated Study Completion Date :

Aug 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

circulating microRNAs in primary hyperparathyroidism patients [2019-2021]
Serum miRNA levels
serum miRNA after parathyroidectomy [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 100 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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