The GranStone Trial
Paraffinoma · Granuloma, Foreign-Body
What this study involves
The registry says this study is recruiting. Individual locations may have different availability.
- Study type
- Interventional
- Phase
- Phase 2 / Phase 3
- Age range
- 18 years - 70 years
- Sex eligible
- Male
- Healthy volunteers
- Not accepted
- Participants
- 100 Estimated
These are starting points, not an eligibility decision. The research team must review the full requirements.
About the research
This study will investigate whether treatment with empagliflozin or losartan can reduce the risk of kidney stone formation in patients with paraffin disease, a condition caused by the injection of paraffin oil into muscle tissue for cosmetic muscle enlargement.
Paraffin disease can lead to chronic inflammation, disturbances in calcium regulation, high blood calcium levels, kidney stones, and impaired kidney function. Previous studies from Herlev-Gentofte Hospital have shown that kidney stones occur in nearly half of affected patients, while approximately one-third develop reduced kidney function. Current treatment primarily consists of high-dose corticosteroids, which can reduce blood calcium levels but cause substantial adverse effects and may not adequately control the underlying disease process.
Both empagliflozin and losartan are widely used medications with documented kidney-protective effects in other chronic kidney diseases. This randomized clinical trial will evaluate whether either treatment can prevent kidney stone formation and slow kidney-related complications in patients with paraffin disease.
The purpose of this study is to determine whether treatment with empagliflozin or losartan can prevent kidney stone formation and improve kidney health in patients with paraffin disease.
Read the full description
Cosmetic treatments are becoming increasingly popular, now also encompassing injection of different sorts of fillers. One such approach is the injection of paraffin oil into muscular regions for the sole purpose of enhancing muscular size. During the last 4 years we have experienced that injections with paraffin oil are being more widely used than anticipated. Usage is mainly seen in the younger segment of the male Danish population, causing severe morbidity including hypercalcemia, kidney stones and renal failure in patients often in their thirties. Injected paraffin oil causes foreign body reactions, leading to inflammation and granuloma formation. Granulomas are rich in macrophages capable of producing large amount of activated vitamin D (1,25OH2D3) that may cause severe hypercalcemia. Although, the link between foreign body granuloma, and hypercalcemia has been known for more than 60 years sparse evidence-based treatments exist to control calcium and vitamin D balance in these patients. Physiologically, cutaneous produced or orally absorbed 25OH2D3 (cholecalciferol) needs activation before it can activate the vitamin D receptor (VDR) and exert its actions. This activation occurs through hydroxylation by CYP27B1 in the kidneys creating the active 1,25(OH)2D3 (calcitriol). CYP27B1 is the rate-limiting step in calcitriol synthesis and is tightly regulated under physiologic conditions. Control of high 1,25(OH)2D3 is achieved by a feedback system, where 1,25(OH)2D3 stimulates the enzyme CYP24A1, which in turn hy-droxylate 1,25(OH)2D3 to the inactive 1,24,25OH2D3. Several other players, e.g. parathy-roid hormone (PTH) and fibroblast growth factor 23 (FGF23) regulate calcium homeostasis. However, in macrophages, CYP27B1 is upregulated by interleukin 2, and the inhibiting enzyme CYP24A1 is not upregulated. Therefore, granulomas can produce large amounts of 1,25OH2D3, and this production is not counteracted by the otherwise tight regulatory and physiological mechanisms. Unimpeded 1,25OH2D3 in turn increase calcium absorption from the intestines, reabsorption from the kidneys and to some extent calcium release from bones, all leading to hypercalcemia. Hypercalcemia is a late feature of accelerated 25OH2D3 activation, as several counter regulatory mechanisms will attempt to maintain normocalcemia. As a result, these patients suffer from nephrolithiasis or progressive kidney disease due to nephrocalcinosis and/or nephrolithiasis, with some patients progressing to end stage renal dis-ease (ESRD).
SGLT2 inhibitors were developed for treatment of type 2 diabetes to lower blood glucose levels but they had a more pronounced effect in patients with heart or renal failure irrespective of diabetes status. SGLT2 inhibitors could prevent or reduce eGFR decline in patients with renal failure and it appeared in some trials that it could also lower the risk of nephrolithiasis. SGLT2 inhibitors have few adverse effects in non-diabetics and may be used to prevent progression of paraffin oil disease by protecting the kidney and reducing the risk of kidney stones in these patients. ACEi's and ARB's have also been shown to reduce progression of kidney disease. Although the data on prevention of kidney stones is less convincing for ACEi/ARB's the renoprotective effects make them a potential treatment option.
Data from our cohort of patients:
During our initial investigation of 88 patients, milder symptoms of hypercalcemia were often accompanied by hypercalcuria with increased risk of kidney stones and later nephrocalcinosis and ultimately progressive renal failure and vascular calcification as seen in patients with primary hyperparathyroidism or CKD. 3 deaths have been recorded in our cohort of young men, so paraffin disease leads to significant morbidity, but presumably also increased mortality. Currently, paraffin disease is still very sparsely described in the medical literature. The number of affected individuals is presumably large because early disease causes few symptoms and many of these men rarely seek medical attention. At the section of Endocrinology at Herlev-Gentofte Hospital, there is currently more than 310 young males who injected paraffin oil prior to referral. In the first published cohort of 88 males (32 ± 7 years (mean ± SD)) who injected paraffin oil 6 years prior to their first visit, the minority (42%) have managed to maintain an apparent normal calcium metabolism (normocalcemic and normoparathyoid), while the majority have developed an abnormal calcium metabolism ranging from normocalcemic and hypoparathyroid (24%) to hypercalcemic and hypoparathyroid (34%). Renal stone formers ranging from 22 % in patients with an apparent normal calcium homeostasis to a stunning 47-48% in those with abnormal calcium homeostasis (5-10% in back-ground population). Importantly, a significant number of patients (approx. 30%) had already developed mild to severe renal impairment with reduced eGFR. Most patients tended to have increased inflammatory markers (interleukine-2 receptor (IL-2R) and/or pepti-dyldipeptidase (ACE)) - even in those with apparent normal calcium metabolism. Surgical resection may improve both local reactions and pain. However, due to granuloma formation within muscle tissue and oilmigration, it is difficult to remove all the granuloma tissue. Currently, first line of treatment for paraffin disease is prednisolone, which has proven effective in lowering calcium levels in all our patients. However, patients require relatively large (15-75 mg daily) and long term (years) doses of prednisolone to achieve and maintain normal or near normal calcium levels with many possible adverse effects. Noteworthy, after 4 years observation we have not yet seen any decrease in inflammatory markers in any male suggesting that prednisolone monotherapy is not enough when you have large amount of granuloma tissue. Paraffin disease mimics sarcoidosis, both being granulomatous diseases with hypercalcemia due to macrophage mediated 25OH2D3 activation. Interestingly, RAAS activation has been shown to contribute to sarcoidosis granuloma formation in an ex vivo model, highlighting an additional potential role for treatment with ACEi/ARB's. However, paraffin disease appears to be much more progressive, not self-limiting and require more aggressive treatment probably because the volume of granulomatous tissue is so huge.
Since ACEi's, ARB's and SGLTi's are the only drug classes consistently shown to slow progression in CKD in a non-diabetic population, we hypothesize that these treatments will be effective in a cohort of patients with hypercalcemia due to paraffin oil induced granulomatous disease. Furthermore, we hypothesize that SGLTi will have a greater effect due to the potential decrease in incident nephrolithiasis. However, the ketosis associated with this treatment may not be beneficial, which clearly justifies the face-to-face comparison.
Losartan was chosen over an ACE inhibitor due to ease of administration and proven safety in patients with severe kidney disease. Additionally, it has been suggested that ARB's have greater efficacy than ACEi's on survival in patients with granulomatous disease due to sarcoidosis.
This research project will investigate whether it is of value to initiate nephroprotective treatment with an SGLT2 inhibitor or ARB in patients with hypercalciuria due to paraffin oil induced granulomatous disease.
Who may be able to participate?
The list below is the sponsor’s full registry wording. It can include conditions, prior treatment, test results and other requirements. A match in search does not mean you qualify.
Inclusion Criteria:
- Signed informed consent by participant
- Male
- 18-70 years
- Paraffin granuloma disease with hypercalcemia, hypoparathyroidism, hypercalciuria or a history of nephrolithiasis
Exclusion Criteria:
- eGFR \< 30 ml/min
- Cancer (past or present, except basal cell skin cancer or squamous cell skin cancer), which in the investigator's opinion could interfere with the results of the trial
- Type 1 DM
- Known chronic kidney disease in whom RAS-blockade and SGLT2-inhibition is indicated.
- Severely impaired liver function
- History of organ transplantation
- Receiving therapy with an SGLT2 inhibitor or ATII antagonist within 8 weeks prior to enrollment or previous intolerance of an SGLT2 inhibitor or ATII antagonist.
- Known history of angioedema
- Mental incapacity, language barriers or unwillingness to comply with the requirements of the protocol, which may preclude adequate understanding or cooperation during the trial, as judged by the investigator
Treatment, groups and participation
The registry may describe treatments and study duration without a complete visit calendar. Ask the study team for the exact schedule, procedures, risks, costs and alternatives. Keep your usual care plan unless your treating clinician tells you otherwise.
- Assignment
- Random assignment
- Masking
- Single masked
Empagliflozin
Once daily 25 mg tablet PO
Drug: empagliflozin (Jardiance) 25 mg
Losartan
Once daily 100 mg tablet PO
Drug: Losartan 100 mg
empagliflozin (Jardiance) 25 mg DRUG
Once daily 25 mg tablet PO
Losartan 100 mg DRUG
Once daily 100 mg tablet PO
What researchers are measuring
Outcome measures describe what is being studied. They are not proof that a treatment works.
Primary measures
Image verified new or increased nephrolithiasis or nephrocalcinosis (from 0-24 months).
Time frame: From baseline to end of follow-up at 24 months
The individual components of the composite outcome are defined as follows:
- If nephrolithiasis- or nephrocalcinosis burden occurs after baseline or aggravates by more than 20% at follow-up it is counted as a positive outcome.
- Any CT scans conducted as a part of a participant's routine medical care or hospital visits will also be used.
- In the event that a participant undergoes more than 1 CT scan, it will be counted as a positive outcome if any of the scans shows nephrolithiasis or nephrocalcinosis accord-ing to the criteria above.
- Symptomatic kidney stone as defined as visible passage of a stone in the urine accom-panied by flank/groin/abdominal pain will also be counted as a positive outcome.
Secondary measures
Change in calcium homeostasis after 12 and 24 months
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Change in calcium homeostasis after 12 and 24 months defined by either: 1A Change in p-Calcium ion concentration (mmol/L); 1B Change in p-PTH concen-tration (pmol/L); 1C Change in urine calcium excretion (mmol/L).
Change in estimated glomerular filtration rate (eGFR) (mL/min/1.73 m²)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Not reported in this registry record.
Change in p-Creatinine (μmol/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Not reported in this registry record.
Change in average daily prednisolone dosage (mg) based on cumulative average prednisolone dose.
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Not reported in this registry record.
Change in inflammatory activity of the granulomas.
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Change in inflammatory activity evaluated by changes in p-IL-2R (kU/L) and p-ACE (U/L).
Change in physical- and mental health scores assessed by the Short-Form 36 questionnaire (SF-36).
Time frame: From baseline to end of follow-up at 24 months
The SF-36 consists of 36 questions designed to assess overall health status. Results are transformed onto a scale from 0 (worst possible health) to 100 (best possible health).
Change in serum albumin (g/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Not reported in this registry record.
Change in urine albumin (mg/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Not reported in this registry record.
Changes in serum vitamin D metabolites
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Changes in serum 25OHD, and 24,25(OH)2D3, and 1,25(OH)2D
Changes in left ventricular ejection fraction (LVEF) and other indices of cardiac function as measured by transthoracic echocardiography.
Time frame: From baseline to end of follow-up at 24 months
Not reported in this registry record.
Incident or worsening signs of: Systolic- and/or diastolic dysfunction, left ventricular hypertrophy, structural heart disease including valvular pathology
Time frame: From baseline to end of follow-up at 24 months
Not reported in this registry record.
Changes in CT Hounsfield Units in the femoral neck and lumbar vertebrae
Time frame: From baseline to end of follow-up at 24 months
Not reported in this registry record.
Change in Coronary Artery Calcium Score on CT-scan
Time frame: From baseline to end of follow-up at 24 months
Coronary artery calcium (CAC) score measured using the Agatston method on non-contrast cardiac CT; higher scores indicate greater coronary calcified plaque burden.
Changes in self-reported kidney stones.
Time frame: From baseline to end of follow-up at 24 months
Not reported in this registry record.
Change in BUN (mmol/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Not reported in this registry record.
Change in serum phosphate (mmol/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Not reported in this registry record.
Change in urine phosphate (mmol/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Not reported in this registry record.
Change in serum magnesium (mmol/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Not reported in this registry record.
Change in urine magnesium (mmol/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Not reported in this registry record.
Change in serum iron (µmol/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Not reported in this registry record.
Change in serum ferritin (µg/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Not reported in this registry record.
Change in serum FGF23 (ng/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Not reported in this registry record.
Change in serum Klotho
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Not reported in this registry record.
Change in urine Ka (mmol/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Not reported in this registry record.
Change in urine Na (mmol/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Not reported in this registry record.
Change in urine pH
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Not reported in this registry record.
Change in urine citrate (mmol/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Not reported in this registry record.
Change in urine oxalate (μmol/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Not reported in this registry record.
Change in urine bicarbonate (mmol/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Not reported in this registry record.
Change in urine uric acid (mmol/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Not reported in this registry record.
Review the complete result tables and limitations in the official record.
Open official results ↗Research locations (1)
The overall study status and a local site’s status can differ. Confirm that location’s availability before traveling.
1 locations
Division of Translational Endocrinology, Department of Endocrinology and Internal Medicine, Copenhagen University Hospital Herlev, HerlevHerlev, DenmarkRecruiting
Study team and timeline
- Lead sponsor
- Martin Blomberg Jensen
- Study start
- Oct 20, 2026 Actual
- Primary completion
- 2029-03 Estimated
- Study completion
- 2029-04 Estimated
- First posted
- Sep 18, 2026 Actual
- Last updated
- Nov 10, 2026 Actual
Official study contacts
Official study title
Prevention of Kidney Stones Due to Paraffin Oil Induced Granuloma: A Prospective Interventional Study
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Source: ClinicalTrials.gov API v2. Information is submitted by sponsors and investigators. NLM does not approve the safety or science of all listed studies. Registry disclaimer.
Retrieved: Nov 12, 2026 · Last registry update: Nov 10, 2026