WHITE CAP: Intra-operative Parathyroid Tissue Sensor (PTS)-Guided Assessment of Parathyroid Viability and Surgical Decision-Making (WHITE CAP-PTS)

WHITE CAP Trial: Optical Parathyroid Tissue Sensor-Guided Assessment of Parathyroid Viability and Its Impact on Clinical Decision-Making

Primary hyperparathyroidism is usually cured by removing the single over-active parathyroid adenoma. During surgery, however, surgeons often see a thin rim of normal parathyroid tissue that still "glows" under a near-infrared parathyroid tissue sensor (PTS). It is unclear whether keeping this tissue in place helps preserve hormone function or whether it leaves behind cells that could become over-active again.

The WHITE CAP study will compare two common surgical choices:

Preservation strategy - the surgeon removes only the adenoma and leaves the glowing rim of normal tissue untouched.

En-bloc strategy - the surgeon removes the adenoma together with the glowing rim; if too little parathyroid tissue remains, a small fragment is transplanted into the forearm muscle.

About 120 adult patients who have a single parathyroid adenoma will be randomly assigned (like tossing a coin) to one of the two strategies. All operations will use the same FDA-cleared PTS camera that shows the glands in real time without dye or radiation.

The main question is whether preserving the normal rim lowers the rate of temporary low blood-calcium (numbness, tingling) during the first two days after surgery. The study will also check long-term results-blood calcium and parathyroid hormone (PTH) levels, symptoms, and any return of the disease-over two years.

The PTS imaging itself is painless and adds only a few minutes to the operation. Risks are the same as for standard parathyroid surgery, and participants can withdraw at any time without affecting their usual care.

Study Overview

• Status: Not yet recruiting
• Conditions: Hyperparathyroidism, Primary; Hypocalcemia; Parathyroid Neoplasms; Parathyroid Adenoma
• Intervention / Treatment: Device: Near-Infrared Parathyroid Tissue Sensor Imaging (PTS); Procedure: Rim-Preservation Technique; Procedure: En-bloc Resection Technique

Detailed Description

Background and Rationale Near-infrared autofluorescence (NIRAF) highlights parathyroid tissue at a wavelength of 820 nm. Several devices, including Fluobeam LX and PTeye®, have FDA 510(k) clearance for intra-operative identification of parathyroid glands. In ~70 % of single-gland disease, NIRAF shows a viable rim of normal tissue partially encasing the adenoma. Retrospective data conflict on whether rim preservation reduces transient hypocalcaemia or increases recurrence. No prospective randomized evidence exists.

Objectives Primary: Compare the incidence of transient hypocalcaemia (albumin-corrected Ca < 2.00 mmol·L-¹ or need for calcium/vit-D supplementation) within 48 h post-operative between preservation and en-bloc strategies.

Secondary: (i) Permanent hypocalcaemia at 6 months; (ii) PTH ≥ 15 pg·mL-¹ at 24 h; (iii) operative time and blood loss; (iv) biochemical or clinical recurrence up to 24 months; (v) correlation of quantitative NIRAF intensity with gland viability.

Study Design Multicentre, parallel-group, 1:1 randomized controlled trial (RCT). Block randomisation (size 4) stratified by centre and baseline vitamin-D status. Total sample 120 participants (60 per arm, includes 10 % attrition). Single-blind: outcome assessors and laboratory staff remain unaware of allocation.

Interventions Preservation arm: After adenoma excision, surgeon confirms NIRAF-positive rim and leaves it in situ; only minimal defatting to ensure vascularity.

En-bloc arm: Adenoma plus NIRAF-positive rim excised en bloc. If fewer than two normal glands remain in the neck, a 30 mg fragment is minced and autotransplanted into the non-dominant brachioradialis.

Eligibility Inclusion: age 18-75 y; biochemically confirmed primary hyperparathyroidism; imaging (MIBI or 4D-CT) concordant with a solitary adenoma; written informed consent.

Exclusion: multiple endocrine neoplasia, >1 enlarged gland on imaging, eGFR < 30, pregnancy, neck re-exploration, planned concomitant total thyroidectomy.

Outcome Assessments Serum Ca, phosphate, Mg, PTH measured pre-op; 6 h, 24 h, 48 h; Day 7; Months 1, 6, 12, 24. Laryngoscopy if voice change occurs. Recurrence defined as Ca above upper limit plus PTH > 65 pg·mL-¹ after Month 12. NIRAF intensity recorded (arbitrary units) using standard ROI software.

Statistical Plan Transient hypocalcaemia expected 30 % in en-bloc vs 10 % in preservation. With α = 0.05, 1-β = 0.80, needs 54 per arm; rounded to 60. Intent-to-treat analysis. Risk ratios with 95 % CI; secondary continuous outcomes by mixed-effects ANCOVA. Interim safety review at 50 % recruitment (O'Brien-Fleming boundary).

Regulatory and Ethics PTS devices are FDA-cleared; study classified as non-significant-risk device research exempt from IDE (21 CFR 812.2(b)). All centres have IRB approval. Data stored in REDCap, anonymised, GDPR-compliant. A three-member DSMB (endocrine surgeon, endocrinologist, biostatistician) will monitor AEs; trial pause if permanent hypocalcaemia exceeds 15 %.

Data Sharing De-identified participant data and analytic code will be available upon reasonable request 6 months after primary publication.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Bo Wang Professor, MD; Phone Number: +13959123550; Email: wangbo@fjmu.edu.cn

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Fujian Medical University Union Hospital
      • Contact: Bo Wang Porfessor, MD; Phone Number: +13959123550; Email: wangbo@fjmu.edu.cn
      • Principal Investigator: Bo Wang MD, Principal Investigator

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18 to 75 years, able to give informed consent.
• Biochemically proven primary hyperparathyroidism (elevated serum calcium and inappropriately high PTH).
• Pre-operative imaging (sestamibi scan, 4-phase CT, or ultrasound) concordant with a single parathyroid adenoma.
• Planned minimally invasive parathyroidectomy using near-infrared parathyroid tissue sensor (PTS) guidance.

Exclusion Criteria:

• Multiple endocrine neoplasia (MEN 1 or 2) or suspicion of multi-gland disease (>1 enlarged gland on imaging).
• Prior parathyroid or extensive neck surgery causing distorted anatomy.
• Need for simultaneous total thyroidectomy or other major neck procedure.
• Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m².
• Pregnancy or breastfeeding.
• Inability to tolerate general anaesthesia or contraindication to intra-operative PTS imaging.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A - Rim Preservation; Participants undergo adenoma removal guided by PTS imaging, with deliberate preservation of the NIR-autofluorescent rim of normal parathyroid tissue.	Device: Near-Infrared Parathyroid Tissue Sensor Imaging (PTS); FDA-cleared imager (e.g., Fluobeam LX/PTeye) providing real-time autofluorescence to identify parathyroid tissue during surgery; no dye or radiation.; Procedure: Rim-Preservation Technique; Surgical excision of adenoma while leaving the NIRAF-positive rim of normal parathyroid tissue in situ; minimal defatting to ensure perfusion.
Active Comparator: Arm B - En-bloc Resection; Participants undergo PTS-guided en-bloc excision of the adenoma plus its NIR-positive rim; parathyroid autotransplantation performed when indicated.	Device: Near-Infrared Parathyroid Tissue Sensor Imaging (PTS); FDA-cleared imager (e.g., Fluobeam LX/PTeye) providing real-time autofluorescence to identify parathyroid tissue during surgery; no dye or radiation.; Procedure: En-bloc Resection Technique; Surgical excision of adenoma together with the surrounding NIRAF-positive rim; autotransplant fragment if < 2 normal glands remain in neck.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Transient Hypocalcaemia	Proportion of participants whose albumin-corrected serum calcium falls < 2.00 mmol/L or who require oral/IV calcium ± active vitamin D to maintain normocalcaemia within 48 h post-operatively. Blood samples at 6 h, 24 h, and 48 h will be analysed by a blinded central laboratory.	Baseline to 48 hours after surgery (Post-op Day 0-2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Permanent Hypocalcaemia	Need for ongoing calcium ± calcitriol to maintain normocalcaemia at ≥ 6 months after surgery.	6 months (±14 days) post-op
Parathyroid Hormone (PTH) Recovery ≥ 15 pg/mL	Percentage of patients with serum PTH ≥ 15 pg/mL at 24 h, indicating preserved parathyroid function.	24 hours post-op
Operative Time	Skin incision to skin closure, recorded by anaesthesia time stamp.	Intra-operative (minutes)
Estimated Blood Loss	Calculated from suction canister minus irrigation plus soaked swab weight.	Intra-operative (mL)
Biochemical or Clinical Recurrence	Recurrence defined as serum calcium above lab upper limit of normal + PTH > 65 pg/mL and/or imaging-confirmed adenoma regrowth.	12 to 24 months post-op
Correlation of NIRAF Intensity with PTH Recovery	Spearman correlation between quantitative NIRAF counts (ROI) and 24-h PTH value.	Intra-op & 24 hours post-op

Collaborators and Investigators

• Sponsor: Fujian Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2025
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: June 21, 2025
• First Submitted That Met QC Criteria: June 27, 2025
• First Posted (Actual): June 29, 2025

Study Record Updates

• Last Update Posted (Actual): June 29, 2025
• Last Update Submitted That Met QC Criteria: June 27, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Near-Infrared Autofluorescence; Parathyroid Tissue Sensor; Parathyroid Viability; Peri-adenoma Rim Preservation; Intra-operative Imaging; Calcium Homeostasis; PTS Camera
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Metabolic Diseases; Neoplasms by Histologic Type; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Water-Electrolyte Imbalance; Parathyroid Diseases; Calcium Metabolism Disorders; Hyperparathyroidism; Hyperparathyroidism, Primary; Adenoma; Parathyroid Neoplasms; Hypocalcemia; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Parathyroid Hormone
• Other Study ID Numbers: WHITECAP-PTS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No