A Phase 2/3 interventional study of empagliflozin (Jardiance) 25 mg and Losartan 100 mg in Paraffinoma and Granuloma, Foreign-Body, sponsored by Martin Blomberg Jensen. Recruiting at 1 site in Denmark. Open to male participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2026-11-10.
Sponsored by Martin Blomberg Jensen · Phase 2/3, Interventional, and Treatment
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.
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.
22 studies on the registry are indexed under Nephrocalcinosis; 8 are open to participants now.
This study's planned enrollment of 100 is above the median of 71 across 10 interventional studies indexed under Nephrocalcinosis.
Browse Nephrocalcinosis studies →Martin Blomberg Jensen is the lead sponsor of 13 studies on the registry; 4 are open to participants now.
Counted across the registry records on this site, refreshed daily.
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.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
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.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Once daily 25 mg tablet PO
Drug: empagliflozin (Jardiance) 25 mg
Once daily 100 mg tablet PO
Drug: Losartan 100 mg
Once daily 25 mg tablet PO
Once daily 100 mg tablet PO
Image verified new or increased nephrolithiasis or nephrocalcinosis (from 0-24 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.
Time frame: From baseline to end of follow-up at 24 months
Change in calcium homeostasis after 12 and 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).
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
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
Change in p-Creatinine (μmol/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
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
Change in inflammatory activity of the granulomas.
Change in inflammatory activity evaluated by changes in p-IL-2R (kU/L) and p-ACE (U/L).
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Change in physical- and mental health scores assessed by the Short-Form 36 questionnaire (SF-36).
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).
Time frame: From baseline to end of follow-up at 24 months
Change in serum albumin (g/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Change in urine albumin (mg/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Changes in serum vitamin D metabolites
Changes in serum 25OHD, and 24,25(OH)2D3, and 1,25(OH)2D
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
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
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
Changes in CT Hounsfield Units in the femoral neck and lumbar vertebrae
Time frame: From baseline to end of follow-up at 24 months
Change in Coronary Artery Calcium Score on CT-scan
Coronary artery calcium (CAC) score measured using the Agatston method on non-contrast cardiac CT; higher scores indicate greater coronary calcified plaque burden.
Time frame: From baseline to end of follow-up at 24 months
Changes in self-reported kidney stones.
Time frame: From baseline to end of follow-up at 24 months
Change in BUN (mmol/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Change in serum phosphate (mmol/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Change in urine phosphate (mmol/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Change in serum magnesium (mmol/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Change in urine magnesium (mmol/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Change in serum iron (µmol/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Change in serum ferritin (µg/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Change in serum FGF23 (ng/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Change in serum Klotho
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Change in urine Ka (mmol/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Change in urine Na (mmol/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Change in urine pH
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Change in urine citrate (mmol/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Change in urine oxalate (μmol/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Change in urine bicarbonate (mmol/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Change in urine uric acid (mmol/L)
Time frame: From baseline to month 3, 12 and end of follow-up at 24 months
Plan to share: No
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 ↗
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Empagliflozin
Martin Blomberg Jensen