An interventional study of Wearable Near-Infrared Autofluorescence Imaging System in Hypocalcemia, Hypoparathyroidism and Thyroid Diseases, sponsored by Ss. Cyril and Methodius University of Skopje. Recruiting at 1 site in North Macedonia. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-11-06.
Sponsored by Ss. Cyril and Methodius University of Skopje · Not applicable, Interventional, and Prevention
This study evaluates whether a wearable near-infrared autofluorescence (NIRAF) imaging system can help surgeons identify and preserve parathyroid glands during thyroid surgery. These small glands produce parathyroid hormone (PTH), which helps control blood calcium. The modified Meta Quest stereoscopic goggles display fluorescence naturally emitted by parathyroid tissue; no injected dye is used.
The study has two components. Component A is a nonrandomized, 30-participant specimen-imaging and pathology-validation component. Component B is a randomized study with a target of 250 adults undergoing total or completion thyroidectomy. Participants in Component B are assigned equally to standard surgery or standard surgery with brief NIRAF imaging of the surgical field and the removed specimen. Clinically appropriate parathyroid rescue and autotransplantation are permitted.
The primary randomized outcome is early biochemical hypoparathyroidism: a serum intact PTH concentration below the testing laboratory's assay-specific lower limit of normal, measured 12 to 24 hours after skin closure, with a target of 18 hours. Calcium levels, later parathyroid function, treatment requirements, surgical findings, and complications are also assessed. Follow-up lasts six months.
Five research blood collections are scheduled: 1 to 2 days before surgery, 12 to 24 hours after surgery, six weeks, three months, and six months. An early safety assessment occurs 48 to 72 hours after surgery. Additional tests and visits are provided whenever clinically needed.
A nested device-performance assessment records additional glands identified beyond the surgeon's initial white-light assessment and documented changes in surgical management attributable to NIRAF information. These findings are assessed separately from the randomized clinical outcomes.
The revised assessment plan will be implemented following documented ethics approval of the amendment.
STUDY COMPONENTS AND DEVICE The investigational platform is a modified Meta Quest head-mounted stereoscopic goggle system configured for label-free near-infrared autofluorescence (NIRAF) imaging, with excitation at approximately 780 nm and detection of parathyroid autofluorescence near 800 nm. No injected contrast agent is used. NIRAF supplements surgical anatomy and clinical judgment; fluorescence does not by itself establish tissue identity, vascular viability, or preserved endocrine function.
Component A is a nonrandomized, 30-participant ex vivo specimen-imaging and pathology-validation component. NIRAF-positive foci on clinically removed thyroidectomy specimens are mapped and correlated with pathology. Available preoperative, early postoperative, and approximately two-month laboratory data are summarized descriptively. Component A participants are not included in the randomized efficacy analysis. No retained parathyroid gland is biopsied for research.
Component B has a fixed target of 250 randomized adults undergoing total or completion thyroidectomy, allocated 1:1 to standard surgery or standard surgery plus NIRAF. This is a feasibility-constrained sample size; detectable effects depend on the actual frequency of the primary outcome. Enrollment in Component A is additional to the randomized target, giving an overall planned enrollment of 280. Participant attribution and analyses follow contemporaneous enrollment records and applicable protocol versions. Revised assessments and outcome definitions will take effect after documented ethics approval of the amendment and from the recorded implementation date. Previously enrolled participants remain accounted for under their applicable protocol versions. Earlier observations are not relabeled as prospectively collected under the revision, and the original outcomes and amendment history will be reported transparently.
OPERATIVE WORKFLOW Both groups receive the same surgeon-led preservation principles, training standards, criteria for conventional rescue/autotransplantation, and postoperative endocrine management. Allocation is concealed until assignment, and the analysis accounts for operating surgeon. In both groups, the surgeon records the glands identified under white light, their locations, confidence in identification, and the intended operative action before the assigned additional assessment. A brief white-light reassessment is performed in the control group and a brief NIRAF assessment at the corresponding surgical stage in the intervention group, early enough to inform preservation before irreversible dissection. Extra dissection solely to find every gland is not required.
In the intervention group, NIRAF imaging of the removed specimen can identify suspected excised parathyroid tissue. Rescue/autotransplantation is performed only when clinically appropriate and oncologically safe. The control group receives standard white-light assessment and conventional rescue when indicated; experimental NIRAF specimen imaging does not guide control-group care. Removed tissue is processed using comparable pathology procedures in both groups. Distinct glands and tissue fragments are recorded separately, together with the reason for removal.
RANDOMIZED CLINICAL OUTCOMES AND FOLLOW-UP The primary outcome is early biochemical hypoparathyroidism, defined as serum intact PTH below the testing laboratory's assay-specific lower limit of normal at 12 to 24 hours after completion of skin closure, targeting 18 hours, regardless of concurrent calcium or symptoms. Before the revised assessments begin, the site documents the testing laboratory, intact PTH assay, units, reference interval, calcium interpretation method, and common management algorithm in the study laboratory/endocrine manual. The assay-specific lower limit of normal is used identically in both randomized groups; no universal numeric PTH cutoff or assay manufacturer is imposed by this registry entry. Any subsequent assay or reference-range change is documented and addressed in the analysis plan. If more than one valid sample is available within the window, the sample closest to 18 hours is used; ties use the earlier sample. A missing in-window sample is not classified as a normal result. Earlier clinically indicated tests do not replace this primary sample.
Five scheduled research blood collections are performed: baseline 1 to 2 days before surgery; 12 to 24 hours after skin closure; day 42 plus or minus 7 days; day 90 plus or minus 14 days; and day 180 plus or minus 21 days. The core panel is intact PTH, total calcium, and albumin. Baseline and six-month panels additionally include magnesium, phosphate, creatinine with estimated glomerular filtration rate, and 25-hydroxyvitamin D. Routine clinical samples meeting these timing and assay requirements can also serve as study samples. No separate routine research blood draw is required at two or four weeks.
A safety assessment occurs at 48 to 72 hours by telephone after discharge or through routine inpatient review. Patients with low PTH, low calcium, symptoms, or replacement treatment receive additional assessment and testing under the common clinical algorithm; they do not wait until the six-week research visit. Day 0 to 30 events are ascertained from records and patient confirmation, which may be completed at the six-week visit. Medication starts, stops, doses, indications, and adherence between visits are recorded. Necessary treatment is never delayed or withheld for research sampling.
The key secondary outcome is biochemical hypoparathyroidism at six weeks, using the same PTH threshold in all randomized participants. Other outcomes include therapeutic active-vitamin-D and oral-calcium treatment days during postoperative days 1 to 90; biochemical and symptomatic hypocalcemia; intravenous calcium and hypocalcemia-related acute-care use; parathyroid tissue excision and autotransplantation; operative time; and surgical or device-related adverse events.
Endocrine status is assessed at three and six months using standardized records reviewed without treatment allocation. Documented normal function or recovery requires PTH and albumin-adjusted calcium within their reference ranges after at least 14 consecutive days without active vitamin D or therapeutic calcium. This is an operational study assessment rule. Treatment withdrawal is attempted only when clinically safe under endocrine supervision; continued prescribing alone does not establish ongoing disease. Cases are classified as documented normal function/recovery, ongoing dysfunction, or indeterminate. Recovery among participants with earlier abnormal findings is reported separately. Dysfunction at six months is not labeled permanent hypoparathyroidism.
DEVICE-PERFORMANCE ASSESSMENT Consecutive goggle-assisted operations are assessed, including procedures with no additional finding and device failures. The principal device-performance measure is the proportion of participants with at least one additional clinically adjudicated parathyroid gland identified beyond the recorded initial white-light assessment. Counts of additional glands are also reported. In situ identity is clinically adjudicated; pathology confirmation is used when tissue has been removed for clinical reasons. Specimen pathology validation is not treated as histological confirmation of every gland preserved in situ.
A clinically significant event (CSE) is new or corrected NIRAF information leading to a documented clinically meaningful change in operative management. Prespecified categories include a change in dissection to preserve a newly identified gland, a corrected tissue identification that changes management, or clinically indicated rescue/autotransplantation after specimen detection. Additional fluorescence or increased confidence without a management change is not, by itself, a CSE. Pre-imaging findings and intended actions, subsequent findings, changed actions or no change, and final gland disposition are documented using operative records and available images, video, and pathology. Independent review applies the prespecified criteria without postoperative endocrine outcomes where feasible. Patient-level CSE proportions and event counts by type are reported; a preservation-related CSE is not interpreted as proof of preserved gland function or prevented hypoparathyroidism.
ANALYSIS AND REPORTING Randomized clinical analyses follow intention to treat, retaining device failures and crossovers in their assigned groups, with prespecified handling of missing outcomes. The primary comparison uses a two-sided 0.05 significance level. The six-week key secondary outcome is tested confirmatorily only if the primary comparison is significant; other outcomes are supportive and reported with effect estimates and confidence intervals. Device-performance reporting is distinct from randomized endocrine efficacy reporting, and publications identify any overlapping participants and protocol versions. An early device report does not constitute a definitive interim test of clinical efficacy. The statistical analysis plan specifies amendment-era handling before further treatment-arm outcome review.
98 studies on the registry are indexed under Hypocalcemia; 16 are open to participants now.
This study's planned enrollment of 280 is above the median of 84 across 66 interventional studies indexed under Hypocalcemia.
Browse Hypocalcemia studies →Ss. Cyril and Methodius University of Skopje is the lead sponsor of 3 studies on the registry; 2 are open to participants now.
Counted across the registry records on this site, refreshed daily.
The criteria were revised on the registry on Nov 6, 2026. See what changed
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants undergo standard thyroidectomy under white light using the same parathyroid-preservation principles, training standards, and postoperative endocrine management as the intervention group. The surgeon records the initial white-light gland assessment and intended action, followed by a brief white-light reassessment at the corresponding stage used for NIRAF assessment in the intervention group. Conventional autotransplantation is permitted when a devascularized or excised gland is identified by standard methods and rescue is clinically appropriate and oncologically safe. Experimental NIRAF imaging does not guide in vivo or specimen-related decisions in this group. Extra dissection solely to identify every gland is not required.
Participants undergo standard thyroidectomy with the same preservation principles and postoperative endocrine management as controls, plus modified Meta Quest NIRAF imaging. The surgeon first records glands identified under white light and the intended operative action. Brief in vivo NIRAF mapping is then performed after exposure, early enough to inform preservation before irreversible dissection, followed by ex vivo imaging of the removed specimen. Additional or corrected findings and resulting management changes are documented for independent CSE review. Rescue/autotransplantation is permitted when clinically appropriate and oncologically safe. Fluorescence alone does not establish tissue identity or vascular viability, and retained glands are not biopsied for research.
Device: Wearable Near-Infrared Autofluorescence Imaging System
A modified Meta Quest head-mounted stereoscopic goggle system configured for label-free near-infrared autofluorescence imaging. The system delivers near-infrared excitation at approximately 780 nm and detects parathyroid autofluorescence centered near 800 nm. No injected dye or external contrast agent is administered. The device is used briefly after thyroid exposure for in vivo mapping and after thyroid resection for ex vivo specimen interrogation.
Also known as: Modified Meta Quest NIRAF goggles
Early Biochemical Hypoparathyroidism After Thyroidectomy (Component B)
Proportion of randomized Component B participants with serum intact PTH below the testing laboratory's assay-specific lower limit of normal, regardless of concurrent calcium or symptoms. The site records the assay, units, and reference interval before revised assessments begin and applies the same interpretation in both groups. No universal numeric cutoff or assay manufacturer is specified. The sample closest to 18 hours within the 12-to-24-hour window is used; ties use the earlier sample. Absence of a valid in-window sample is missing, not normal. Necessary calcium or active-vitamin-D treatment is not withheld for sampling; dose and timing are recorded. This is the sole randomized primary outcome.
Time frame: 12 to 24 hours after completion of skin closure; target 18 hours
Biochemical Hypoparathyroidism at Six Weeks (Component B)
Proportion of all randomized Component B participants with intact PTH below the same prespecified assay-specific lower limit of normal used for the primary endpoint, regardless of their initial postoperative PTH status. This is the key secondary outcome. Confirmatory testing at a two-sided 0.05 level follows a fixed sequence and occurs only if the primary comparison is statistically significant; estimates and confidence intervals are reported regardless.
Time frame: Six weeks after surgery: postoperative day 42 plus or minus 7 days
Pathology-Confirmed Parathyroid Tissue Excision (Component B)
Proportion of randomized Component B participants with histologically confirmed parathyroid tissue in material removed during the index operation. Clinically removed tissue is processed comparably in both groups, with pathology review masked to allocation where feasible. Counts of distinct glands and tissue fragments are reported separately, as are removal reasons, including deliberate, unavoidable, or inadvertent excision. No retained gland is biopsied for research.
Time frame: Index operation, with final pathology review within 30 days after surgery
Early Biochemical Hypocalcemia (Component B)
Proportion of randomized Component B participants with albumin-adjusted total calcium below the prespecified laboratory lower limit of normal in the primary 12-to-24-hour postoperative blood sample. The laboratory reference range and calcium adjustment method are fixed before implementation and used identically in both groups. Symptoms and calcium/active-vitamin-D treatment at sampling are recorded separately.
Time frame: 12 to 24 hours after completion of skin closure; target 18 hours
Parathyroid Functional Status and Documented Recovery (Component B)
Proportions of randomized Component B participants classified at each assessment as documented normal function/recovery, ongoing dysfunction, or indeterminate by endocrine review masked to allocation. Normal function/recovery requires intact PTH and albumin-adjusted calcium within their reference ranges after at least 14 consecutive days without active vitamin D or therapeutic calcium. This is an operational study assessment rule; withdrawal is considered only when clinically safe under endocrine supervision. Continued prescribing alone does not establish dysfunction. Recovery is also summarized among participants with earlier postoperative dysfunction. Six-month dysfunction is not labeled permanent hypoparathyroidism.
Time frame: Three months (day 90 plus or minus 14 days) and six months (day 180 plus or minus 21 days) after surgery
Cumulative Therapeutic Active-Vitamin-D Treatment Days (Component B)
Number of postoperative days on which each randomized Component B participant actually takes therapeutic active vitamin D, such as calcitriol or alfacalcidol, for postoperative parathyroid dysfunction. Agent, dose, indication, and reported adherence are recorded. Prophylactic use is distinguished from therapeutic use; nutritional vitamin D is excluded. Confirmed absence of therapeutic use contributes zero days. Treatment initiation and taper follow the same clinical algorithm in both groups.
Time frame: Postoperative days 1 through 90
Symptomatic Hypocalcemia (Component B)
Proportion of randomized Component B participants with new symptoms or signs attributed to hypocalcemia and contemporaneous biochemical confirmation of low calcium under prespecified clinical criteria. Episodes lacking biochemical confirmation are recorded separately. Events are ascertained from clinical records and patient confirmation; collection may be completed at the six-week visit without changing the 30-day event window.
Time frame: From surgery through postoperative day 30
Cumulative Therapeutic Oral-Calcium Treatment Days (Component B)
Number of postoperative days on which each randomized Component B participant actually takes therapeutic oral calcium for postoperative parathyroid dysfunction. Elemental-calcium dose, indication, and reported adherence are recorded. Prophylactic use is distinguished from therapeutic use; dietary calcium is excluded. Confirmed absence of therapeutic use contributes zero days. Treatment initiation and taper follow the same clinical algorithm in both groups.
Time frame: Postoperative days 1 through 90
Hypocalcemia-Related Emergency-Department Attendance (Component B)
Proportion of randomized Component B participants with at least one emergency-department attendance attributed to hypocalcemia. Event dates, indications, and number of attendances are recorded from clinical records and patient confirmation. Hospital readmissions are reported as a separate outcome. Ascertainment may be completed at the six-week visit without changing the 30-day event window.
Time frame: From surgery through postoperative day 30
Operative Time (Component B)
Duration of the index thyroid operation in minutes, measured from initial incision to completion of skin closure, for each randomized Component B participant. NIRAF mapping time is recorded separately.
Time frame: Index operation
Parathyroid Autotransplantation (Component B)
Proportion of randomized Component B participants undergoing clinically indicated parathyroid autotransplantation during the index operation. Reason, detection method, tissue source, implant site, number of distinct glands when determinable, and number of fragments implanted are recorded separately. Conventional and NIRAF-prompted rescue are distinguished. Autotransplantation alone does not establish later graft function.
Time frame: During the index operation
Hypocalcemia-Related Hospital Readmission (Component B)
Proportion of randomized Component B participants with at least one unplanned hospital readmission attributed to hypocalcemia. Dates, indications, and numbers of admissions are recorded using clinical records and patient confirmation. Emergency-department attendance without admission is recorded separately. Ascertainment may be completed at the six-week visit without changing the 30-day event window.
Time frame: From surgery through postoperative day 30
Intravenous Calcium Treatment (Component B)
Proportion of randomized Component B participants receiving intravenous calcium for postoperative hypocalcemia. Treatment indication, dates, doses, and care setting are recorded. Both groups follow the same clinical treatment algorithm.
Time frame: From surgery through postoperative day 30
Postoperative Bleeding Requiring Intervention (Component B)
Proportion of randomized Component B participants with postoperative bleeding or neck hematoma requiring a clinical intervention, including operative evacuation or another documented therapeutic procedure. Event date, severity, and intervention are recorded; subsequent resolution is followed clinically.
Time frame: From surgery through postoperative day 30; resolution followed through six months
New Vocal-Fold Dysfunction (Component B)
Proportion of randomized Component B participants with new postoperative vocal-fold dysfunction confirmed by laryngoscopy, interpreted relative to preoperative vocal-fold status. Laterality, date of detection, and subsequent recovery are documented. Cases lacking adequate baseline or confirmatory assessment are identified separately.
Time frame: Detected from surgery through postoperative day 30; recovery assessed through six months
Device Failure or Interruption (Component B)
Proportion of intervention-group participants with a device failure or interruption that prevents or disrupts the planned NIRAF assessment. Type, duration, reason, mitigation, and whether the operation continues without device guidance are documented. Failures and interruptions are also reported separately, and affected participants remain in the randomized intention-to-treat analysis.
Time frame: During the index operation
Device-Related Adverse Events (Component B)
Proportion of intervention-group participants with at least one adverse event assessed as related to the investigational NIRAF imaging system. Event type, onset, severity, seriousness, relatedness, action taken, and outcome are recorded. All other surgical adverse events are collected under the common safety procedures in both groups.
Time frame: From the index operation through the six-month assessment (day 180 plus or minus 21 days)
Biochemical Hypocalcemia at Follow-Up (Component B)
Proportion of randomized Component B participants with albumin-adjusted total calcium below the prespecified laboratory lower limit of normal at each scheduled follow-up assessment, reported separately by time point. The calcium adjustment method is fixed and applied identically in both groups. Treatment at sampling and intervening clinically documented hypocalcemic episodes are recorded.
Time frame: Six weeks (day 42 plus or minus 7), three months (day 90 plus or minus 14), and six months (day 180 plus or minus 21) after surgery
NIRAF-Associated Clinically Significant Events (Component B)
Proportion of intervention-group participants with at least one independently adjudicated clinically significant event (CSE): new or corrected NIRAF information producing a documented clinically meaningful change in operative management. Categories include altered dissection to preserve an additional gland, corrected tissue identification that changes management, and clinically indicated rescue/autotransplantation after specimen detection. Additional fluorescence or confidence without a management change is not a CSE. Review uses pre-imaging findings and intended actions, subsequent findings, changed actions, final disposition, and supporting records without postoperative endocrine outcomes where feasible. Consecutive intervention cases, including failures and no-change cases, are accounted for; missing documentation is reported. Event counts by category are summarized. This is a key device-performance endpoint, supportive to the randomized clinical primary endpoint.
Time frame: Events during the index operation; adjudication using operative records and available pathology within 30 days
Total Clinically Adjudicated Parathyroid Mapping Yield (Component B)
Number of distinct clinically adjudicated parathyroid glands identified per intervention-group participant during white-light and NIRAF assessment, with the identification method recorded. Fluorescent sites not adjudicated as parathyroid are reported separately. Participants with no additional finding and device failures remain documented. Gland counts are summarized at participant level; tissue fragments are not counted as separate glands.
Time frame: During the index operation
Additional Parathyroid Identification Beyond Initial White-Light Assessment (Component B)
Proportion of intervention-group participants with at least one additional clinically adjudicated parathyroid gland identified with NIRAF beyond the surgeon's recorded initial white-light declaration. This is the principal endpoint of the nested device-performance assessment, not an additional randomized primary endpoint. Consecutive assigned intervention cases, including no additional findings and device failures, are accounted for. In situ identity is clinically adjudicated; pathology is used only for tissue removed for clinical reasons. Missing documentation is reported separately. Additional identification alone does not establish a CSE or preserved endocrine function.
Time frame: During the index operation
NIRAF Mapping Duration and Time to First Gland Identification (Component B)
Elapsed time from the start of NIRAF assessment to the first clinically adjudicated parathyroid identification, and total NIRAF mapping duration, reported separately in seconds for intervention-group participants. Cases with no gland identified are reported explicitly rather than assigned a zero identification time. Device interruptions and failed assessments are recorded.
Time frame: During the index operation
Exploratory Pathology Confirmation of Marked NIRAF-Positive Foci (Component A)
Descriptive proportion of ex vivo NIRAF-positive, suture-marked foci from Component A that routine or targeted pathology confirms as parathyroid tissue. Denominator: marked foci with an interpretable pathology result; numerator: confirmed parathyroid foci. Participant-level counts and uninterpretable or missing results are also summarized. This exploratory registry measure is added after study initiation; reporting identifies the applicable protocol and observation dates. It does not estimate sensitivity or specificity and does not validate the identity of every gland preserved in situ.
Time frame: Index operation and pathology review within 30 days
Number of Additional Parathyroid Glands Identified (Component B)
Number of distinct additional clinically adjudicated parathyroid glands identified with NIRAF beyond the surgeon's recorded initial white-light declaration, per intervention-group participant. A documented absence of additional glands contributes zero. Uncertain identity, tissue fragments, and missing documentation are distinguished. Participant-level distributions are reported; glands are not treated as independent participants.
Time frame: During the index operation
Plan to share: No — No individual participant data will be shared with outside researchers. Deidentified aggregate study results may be reported in scientific presentations and publications.
Started Sep 2026 (actual). Primary completion is estimated for Jun 2029, 33 months after the start.
Of 20 interventional studies with no phase under Hypocalcemia, half reached primary completion within 23 months of starting (the median), counting those still running; a quarter within 16 and three quarters within 39. This study's planned 33 months is above that.
Start moved once since we started tracking on Sep 25, 2026: Jun 2026 → Sep 2026, on Nov 6, 2026.
Earlier changes are on the record history on ClinicalTrials.gov ↗
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Ss. Cyril and Methodius University of Skopje