Chronic Kidney Disease Mineral and Bone DisorderREPAIR-CKDNCT07171216
The Effect of REgulation of PArathyroId hoRmone in Patients With Chronic Kidney Disease to Investigate the Change in Bone Mineral Density
A study testing Treat to target in people with Chronic Kidney Disease Mineral and Bone Disorder, run by Herlev Hospital at 1 site in Denmark.
Trial summary
The prevalence of chronic kidney disease (CKD) in the adult population is estimated to 10%. CKD increases risk of bone fractures, cardiovascular disease and death. The main role of parathyroid hormone (PTH) is to regulate mineral metabolism, including the calcium and phosphate homeostasis. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Chronic Kidney Disease Mineral and Bone Disorder
- What is being tested?
- Treat to target
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteDenmark
- Study dates
- 20 Nov 2025to 1 Sep 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥50 years of age at screening
- CKD G4-5nonD (eGFR < 30 mL/min/1.73m2) based on local laboratory assessment of serum creatinine and eGFR estimated by the CKD-EPI formula)
- Plasma PTH > upper normal limit of local laboratory reference range (> 8,5µmol/L) and/or treated with active vitamin D (Alphacalcidol) or calcimetics (Cinacalcet) initially
- Written informed consent
Who cannot join
- Patients who have received a kidney transplant
- Patients receiving treatment with specific anti-osteoporosis medication (denosumab/bisphosphonates) (because of the profound effect on calcium/phosphate fluxes and BMD)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Denmark1 site, 1 recruiting
- Recruiting
Department of Nephrology, outpatient clinic, Herlev Hospital
Herlev, Capital Region, 2730
Freja S Hassager, Medical doctor, 0045+22554707, freja.staehr.hassager.01@regionh.dk
Freja S Hassager, Medical doctor
About this study
Official title: The Effect of REgulation of PArathyroId hoRmone in Patients With Chronic Kidney Disease to Investigate the Change in Bone Mineral Density (Biskjoldbruskkirtelhormon og knogletæthed Hos Patienter Med Kronisk Nyresygdom)
The prevalence of chronic kidney disease (CKD) in the adult population is estimated to 10%. CKD increases risk of bone fractures, cardiovascular disease and death. The main role of parathyroid hormone (PTH) is to regulate mineral metabolism, including the calcium and phosphate homeostasis. PTH increases as the kidney function declines, and at end stage kidney disease almost all patients have disturbances in the mineral metabolism. Decreasing bone mineral density is associated with risk of fracture, both in background population and in patients with CKD.
For decades, treatment with activated vitamin D, phosphate binders, and calcium supplements has been used for patients with chronic kidney disease and elevated parathyroid hormone, but treatment targets have varied greatly over the years, reflecting the lack of randomized clinical trials with clinical important end points.
Read more
The purpose of The REPAIR-CKD trial is to determine if treatment of hyperparathyroidism improves the bone mineral density in patients with chronic kidney disease.
During this trial it will also be evaluated if it is feasible to obtain a difference in PTH levels when targeting two different levels of PTH.
Further this trial will explore if a difference in PTH influences on arterial stiffness, muscle mass, muscle function, bone histology and health related quality of life.
Read the detailed description
The prevalence of chronic kidney disease (CKD) is estimated to afflict 10 % of the adult population, and it is increasing world-wide. CKD is a devastating disease due to the risk of kidney failure and thereby the need for dialysis or transplantation, but also because the presence of CKD increases the risk of bone fracture, cardiovascular disease and mortality.
Parathyroid hormone (PTH) is a peptide hormone produced by the parathyroid glands(5). The main function of PTH is to regulate mineral metabolism, including the calcium and phosphate homeostasis. PTH increases as the kidney function declines, and at end stage kidney disease almost all patients have disturbances in the mineral metabolism. Treatment with activated vitamin D, phosphate binder and calcium supplementation has been used for more than 30 years to suppress hyperparathyroidism and keep calcium and phosphate within the normal range. Later calcimetics has been introduced as a treatment for secondary hyperparathyroidism.
The risk of bone fracture is increased in patients with CKD and the risk increases as the kidney function declines. A bone fracture leads to a direct burden on the individual. In addition, the risk of complications after a bone fracture is higher in the CKD population compared to the general population. A fracture also constitutes a significant cost for the society. The increased risk of fracture in patients with CKD is associated to the presence of hyperparathyroidism.
Bone mineral density (BMD) assessed by dual energy x-ray (DXA) scan is a highly used modality to diagnose osteoporosis and future fracture risk in the general population. Bone mineral density associates with the risk of future fracture in patients with CKD. In patients with CKD there is an association between decreasing eGFR and both low BMD and future fracture risk. It is unknown how elevated PTH associates with BMD and its changes at different stages of CKD, and it is unknown if treatment of hyperparathyroidism influence on BMD and fracture risk in patients with CKD.
The risk of cardiovascular mortality, coronary heart disease, heart failure, stroke and peripheral arterial disease increase as the kidney function declines. Elevated PTH associates with an increased risk of cardiovascular disease. However, hyperparathyroidism is tightly connected to the general disturbances in the mineral metabolism in CKD, i.e. hyperphosphatemia and elevated FGF-23, which associate with an increased risk of cardiovascular disease and mortality. Therefore, it is questioned if PTH is directly involved in the pathogenesis of cardiovascular disease, or if the increased risk of cardiovascular disease could be caused by other factors involved in the mineral metabolism. One way to approach precursors of vascular disease is measuring vascular stiffness with pulse wave velocity which is associated with cardiovascular outcomes in patients with CKD.
The active circulating form of vitamin D is 1,25 dihydroxy vitamin D (calcitriol). The level of calcitriol is regulated by the activity of the 1α hydroxylase enzyme located in the kidney. The 1α hydroxylase enzyme hydroxylate 25-hydroxy vitamin D at the 1-position. As kidney function declines the activity of 1α hydroxylase is reduced and thereby the circulating level of calcitriol is reduced. The reduced level of calcitriol, together with hypocalcaemia and hyperphosphatemia, leads to secondary hyperparathyroidism. Activated vitamin D is given to patients with hyperparathyroidism to try lowering PTH. In a randomized placebo-controlled trial with 36 patients with CKD G3-5 the intervention group were treated with active vitamin D, which resulted in a difference in BMD by +4.2% in the spine compared to controls after 18 months (P< 0.05). No clinical trials have aimed to explore the influence of targeting different levels of PTH and the influence on bone mineral density or bone fracture in patients with CKD.
Two randomized placebo-controlled trials aimed to address effect of 1 year of active vitamin D treatment on the left ventricular mass, a surrogate endpoint for development of heart failure. No difference between the treatment groups was found in any of the trials. Cohort studies in dialysis patients have found increased survival in patients treated with active vitamin D, but the result could be biased having the design in mind. One Japanese randomized controlled trial compared alfacalcidol with placebo in 976 patients on dialysis. Of importance, not all the included participants did have hyperparathyroidism. No difference was found in fatal and non-fatal cardiovascular events, additionally no difference was found in risk of fracture during the study. If this finding would have differed in patients with hyperparathyroidism or in patients with earlier stages of kidney disease and thereby preventable progression of vascular calcification, remains to be determined.
Treatment with active vitamin D, phosphate binders and calcimetics has been used for patients with CKD for decades. Recommendations regarding the appropriate dose and PTH target for different stages of CKD has varied during years and between guidelines, reflecting the lack of randomized clinical trials with clinical important end points.
In patients with CKD G3b-5, it is currently recommended to monitor the PTH every 3-6 month. As more than 50 % of the patients have elevated PTH already at CKD G3b, it is an everyday consideration for the clinician if the patients should be treated to reduce PTH. This is both time- and cost consuming. At present, there is no evidence to advise if secondary hyperparathyroidism should be treated in patients with CKD.
To improve knowledge about when secondary hyperparathyroidism should be treated, investigators want to conduct a randomized clinical trial with one group of patients being treated if PTH is elevated versus a second group of patients not being treated if PTH is elevated.
The investigators hypothesize that suppression of initially elevated PTH will improve BMD, arterial stiffness, muscle mass and muscle strength in patients with CKD.
Subjects will be recruited from the patient population in the outpatient clinic at the Department of Nephrology at Herlev and Gentofte Hospital, Herlev, Denmark.
- Being tested
- Treat to target
- Keywords
- parathyroid hormone, chronic kidney disease, randomized clinical trial, Activated vitamin D
- Medical subject headings
- Chronic Kidney Disease-Mineral and Bone Disorder, Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Treat to targetOther
Participants will receive treatment from a "toolbox" depending on the situation to reach the PTH target. Available medication is mirroring what is used in the outpatient clinic setting already (native vitamin D, activated vitamin D, phosphate binders, calcimetics).
| Study group | Role | What they receive |
|---|---|---|
| PTH intensive target | Experimental | Intensive parathyroid hormone target (within interval of lower and upper normal limits = 2,0 - 8,5 µmol/L). In the intensive PTH target group, treatment will be initiated as soon as the PTH rise above the upper limit of normal. Participants in this group will receive treatment to lower PTH level (activated vitamin D, phosphate binder, native vitamin D and calcimetics).
PTH will be measured as intact PTH with Atellica IM PTH assay at Herlev Hospital laboratory (normal range 2,0 - 8,5 µmol/L). Receives: Other: Treat to target |
| PTH liberal target | Experimental | Liberal parathyroid hormone target (< 5 x upper normal limit = 42,5 µmol/L). In the liberal PTH target group, treatment will not be initiated until PTH rise above five times the upper limit of normal. This is expected to be a small part of the participants.
The cut-off for the liberal PTH target (<5 x upper normal limit) was discussed in the national CKD-MBD group. It is chosen to allow the clinician initiate treatment if PTH reaches unusually high levels, no studies have focussed on PTH-targets before, consequently the cut-off is chosen as part of the pragmatic design. Receives: Other: Treat to target |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in percent change in bone mineral density (BMD) between the treatment groups.
Measured with DEXA-scan
Measured: From baseline to final follow-up at 18 months
Secondary outcomes (9)
Difference in follow-up BMD between treatment groups
Measured with DEXA-scan
Measured: From baseline to final follow-up at 18 months
Difference in follow-up arterial stiffness between the treatment groups
Measured as pulse wave velocity by applanation tonometry with Sphygmocor
Measured: From baseline to final follow-up at 18 months
Difference in follow-up muscle mass between the treatment groups
Measured as appendicular lean body mass (DEXA-scan) as an approximation of muscle mass
Measured: From baseline to final follow-up at 18 months
Difference in follow-up hand grip strenght between the treatment groups
Muscle function will be assessed by different measures including hand grip strenght.
Measured: From baseline to final follow-up at 18 months
Difference in follow-up 10 meter walk test between the treatment groups
Muscle function will be assessed by different measures including 10 meter walk test.
Measured: From baseline to final follow-up at 18 months
Difference in follow-up sit-to-stand test between the treatment groups
Muscle function will be assessed by different measures including sit-to-stand test.
Measured: From baseline to final follow-up at 18 months
Differences in bone histology between the treatment groups
Tetracycline labelled bone biopsy is performed by a trained physician experienced in performing bone biopsies from the iliac crest after a standardised procedure. At randomisation, we will start with a single labelling of the bone with tetracycline, for us to be able to tell how the bone was at the time of randomisation. Before the biopsy procedure the bone is again labelled with tetracycline
Measured: Labelling at baseline and repeated labelling and biopsy at 18 months
Differences in follow-up health-related quality of life between the treatment groups
Health related quality of life will be evaluated through questionnaire "Kidney Disease and Quality of Life" (KDQOL-SF1.3, Danish version).
Measured: From baseline to final follow-up at 18 months
Differences in number of spinal fractures between the treatment groups
Evaluated with DEXA-scan
Measured: From baseline to final follow-up at 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2025
- Study start20 Nov 2025
- Primary completion1 Sep 2027 (estimated)
- Study completion1 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (42)Papers the sponsor has linked to this study.
- Other trials for Chronic Kidney Disease Mineral and Bone DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Intervention in both treatment groups is used to reach a target of PTH (different levels in different groups, no pre-defined treatment)
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Herlev Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Freja Stæhr Hassager, Herlev and Gentofte Hospital
- Investigators
- Ditte Hansen, Medical doctor, professor, Study director, Department of Nephrology, Herlev Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07171216
- Sponsor's protocol ID
- H-25038403
- Acronym
- REPAIR-CKD
- Status last verified
- Sep 2025
- First submitted
- 29 Aug 2025
- Last updated
- 6 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: We do not plan to share IPD as the trial will be conducted according to local legislation (Databeskyttelsesloven, Databeskyttelsesforordningen and Sundhedsloven), which does not allow sharing data.
Publications
Rao SD, Matkovic V, Duncan H. Transiliac bone biopsy. Complications and diagnostic value. Henry Ford Hosp Med J. 1980;28(2-3):112-5. No abstract available.
PubMed 7287505Blake GM, Naeem M, Boutros M. Comparison of effective dose to children and adults from dual X-ray absorptiometry examinations. Bone. 2006 Jun;38(6):935-42. doi: 10.1016/j.bone.2005.11.007. Epub 2005 Dec 22.
PubMed 16376161Njeh CF, Fuerst T, Hans D, Blake GM, Genant HK. Radiation exposure in bone mineral density assessment. Appl Radiat Isot. 1999 Jan;50(1):215-36. doi: 10.1016/s0969-8043(98)00026-8.
PubMed 10028639https://www.fda.gov/media/175746/download
Frimodt-Moller M, Nielsen AH, Kamper AL, Strandgaard S. Reproducibility of pulse-wave analysis and pulse-wave velocity determination in chronic kidney disease. Nephrol Dial Transplant. 2008 Feb;23(2):594-600. doi: 10.1093/ndt/gfm470. Epub 2007 Nov 7.
PubMed 17989106Saag KG, Petersen J, Brandi ML, Karaplis AC, Lorentzon M, Thomas T, Maddox J, Fan M, Meisner PD, Grauer A. Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis. N Engl J Med. 2017 Oct 12;377(15):1417-1427. doi: 10.1056/NEJMoa1708322. Epub 2017 Sep 11.
PubMed 28892457Malluche HH, Monier-Faugere MC, Blomquist G, Davenport DL. Two-year cortical and trabecular bone loss in CKD-5D: biochemical and clinical predictors. Osteoporos Int. 2018 Jan;29(1):125-134. doi: 10.1007/s00198-017-4228-4. Epub 2017 Oct 9.
PubMed 28993865Kang DH, Park CH, Kim HW, Park JT, Han SH, Kim J, Jeong JC, Kim Y, Kim SW, Oh KH, Kang SW, Yoo TH. Kidney function and bone mineral density in chronic kidney disease patients. Clin Kidney J. 2024 Aug 13;17(9):sfae248. doi: 10.1093/ckj/sfae248. eCollection 2024 Sep.
PubMed 40034486Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl. 2009 Aug;(113):S1-130. doi: 10.1038/ki.2009.188.
PubMed 19644521Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group. KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl (2011). 2017 Jul;7(1):1-59. doi: 10.1016/j.kisu.2017.04.001. Epub 2017 Jun 21. No abstract available.
PubMed 30675420J-DAVID Investigators; Shoji T, Inaba M, Fukagawa M, Ando R, Emoto M, Fujii H, Fujimori A, Fukui M, Hase H, Hashimoto T, Hirakata H, Honda H, Hosoya T, Ikari Y, Inaguma D, Inoue T, Isaka Y, Iseki K, Ishimura E, Itami N, Ito C, Kakuta T, Kawai T, Kawanishi H, Kobayashi S, Kumagai J, Maekawa K, Masakane I, Minakuchi J, Mitsuiki K, Mizuguchi T, Morimoto S, Murohara T, Nakatani T, Negi S, Nishi S, Nishikawa M, Ogawa T, Ohta K, Ohtake T, Okamura M, Okuno S, Shigematsu T, Sugimoto T, Suzuki M, Tahara H, Takemoto Y, Tanaka K, Tominaga Y, Tsubakihara Y, Tsujimoto Y, Tsuruya K, Ueda S, Watanabe Y, Yamagata K, Yamakawa T, Yano S, Yokoyama K, Yorioka N, Yoshiyama M, Nishizawa Y. Effect of Oral Alfacalcidol on Clinical Outcomes in Patients Without Secondary Hyperparathyroidism Receiving Maintenance Hemodialysis: The J-DAVID Randomized Clinical Trial. JAMA. 2018 Dec 11;320(22):2325-2334. doi: 10.1001/jama.2018.17749.
PubMed 30535217Teng M, Wolf M, Ofsthun MN, Lazarus JM, Hernan MA, Camargo CA Jr, Thadhani R. Activated injectable vitamin D and hemodialysis survival: a historical cohort study. J Am Soc Nephrol. 2005 Apr;16(4):1115-25. doi: 10.1681/ASN.2004070573. Epub 2005 Feb 23.
PubMed 15728786Thadhani R, Appelbaum E, Pritchett Y, Chang Y, Wenger J, Tamez H, Bhan I, Agarwal R, Zoccali C, Wanner C, Lloyd-Jones D, Cannata J, Thompson BT, Andress D, Zhang W, Packham D, Singh B, Zehnder D, Shah A, Pachika A, Manning WJ, Solomon SD. Vitamin D therapy and cardiac structure and function in patients with chronic kidney disease: the PRIMO randomized controlled trial. JAMA. 2012 Feb 15;307(7):674-84. doi: 10.1001/jama.2012.120.
PubMed 22337679Wang AY, Fang F, Chan J, Wen YY, Qing S, Chan IH, Lo G, Lai KN, Lo WK, Lam CW, Yu CM. Effect of paricalcitol on left ventricular mass and function in CKD--the OPERA trial. J Am Soc Nephrol. 2014 Jan;25(1):175-86. doi: 10.1681/ASN.2013010103. Epub 2013 Sep 19.
PubMed 24052631Rix M, Eskildsen P, Olgaard K. Effect of 18 months of treatment with alfacalcidol on bone in patients with mild to moderate chronic renal failure. Nephrol Dial Transplant. 2004 Apr;19(4):870-6. doi: 10.1093/ndt/gfg595.
PubMed 15031343
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of REgulation of PArathyroId hoRmone in Patients With Chronic Kidney Disease to Investigate the Change in Bone Mineral Density (Biskjoldbruskkirtelhormon og knogletæthed Hos Patienter Med Kronisk Nyresygdom)
- ClinicalTrials.gov ID
- NCT07171216
- Acronym / sponsor ID
- REPAIR-CKD / H-25038403
- Keywords
- parathyroid hormone, chronic kidney disease, randomized clinical trial, Activated vitamin D
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Herlev HospitalUniversity, hospital or other
- Study start
- 20 Nov 2025 (actual)
- Primary completion
- 1 Sep 2027 (estimated)
- Study completion
- 1 Sep 2027 (estimated)
- First posted
- 12 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The prevalence of chronic kidney disease (CKD) in the adult population is estimated to 10%. CKD increases risk of bone fractures, cardiovascular disease and death. The main role of parathyroid hormone (PTH) is to regulate mineral metabolism, including the calcium and phosphate homeostasis. PTH increases as the kidney function declines, and at end stage kidney disease almost all patients have disturbances in the mineral metabolism. Decreasing bone mineral density is associated with risk of fracture, both in background population and in patients with CKD.
For decades, treatment with activated vitamin D, phosphate binders, and calcium supplements has been used for patients with chronic kidney disease and elevated parathyroid hormone, but treatment targets have varied greatly over the years, reflecting the lack of randomized clinical trials with clinical important end points.
The purpose of The REPAIR-CKD trial is to determine if treatment of hyperparathyroidism improves the bone mineral density in patients with chronic kidney disease.
During this trial it will also be evaluated if it is feasible to obtain a difference in PTH levels when targeting two different levels of PTH.
Further this trial will explore if a difference in PTH influences on arterial stiffness, muscle mass, muscle function, bone histology and health related quality of life.
Detailed description
The prevalence of chronic kidney disease (CKD) is estimated to afflict 10 % of the adult population, and it is increasing world-wide. CKD is a devastating disease due to the risk of kidney failure and thereby the need for dialysis or transplantation, but also because the presence of CKD increases the risk of bone fracture, cardiovascular disease and mortality.
Parathyroid hormone (PTH) is a peptide hormone produced by the parathyroid glands(5). The main function of PTH is to regulate mineral metabolism, including the calcium and phosphate homeostasis. PTH increases as the kidney function declines, and at end stage kidney disease almost all patients have disturbances in the mineral metabolism. Treatment with activated vitamin D, phosphate binder and calcium supplementation has been used for more than 30 years to suppress hyperparathyroidism and keep calcium and phosphate within the normal range. Later calcimetics has been introduced as a treatment for secondary hyperparathyroidism.
The risk of bone fracture is increased in patients with CKD and the risk increases as the kidney function declines. A bone fracture leads to a direct burden on the individual. In addition, the risk of complications after a bone fracture is higher in the CKD population compared to the general population. A fracture also constitutes a significant cost for the society. The increased risk of fracture in patients with CKD is associated to the presence of hyperparathyroidism.
Bone mineral density (BMD) assessed by dual energy x-ray (DXA) scan is a highly used modality to diagnose osteoporosis and future fracture risk in the general population. Bone mineral density associates with the risk of future fracture in patients with CKD. In patients with CKD there is an association between decreasing eGFR and both low BMD and future fracture risk. It is unknown how elevated PTH associates with BMD and its changes at different stages of CKD, and it is unknown if treatment of hyperparathyroidism influence on BMD and fracture risk in patients with CKD.
The risk of cardiovascular mortality, coronary heart disease, heart failure, stroke and peripheral arterial disease increase as the kidney function declines. Elevated PTH associates with an increased risk of cardiovascular disease. However, hyperparathyroidism is tightly connected to the general disturbances in the mineral metabolism in CKD, i.e. hyperphosphatemia and elevated FGF-23, which associate with an increased risk of cardiovascular disease and mortality. Therefore, it is questioned if PTH is directly involved in the pathogenesis of cardiovascular disease, or if the increased risk of cardiovascular disease could be caused by other factors involved in the mineral metabolism. One way to approach precursors of vascular disease is measuring vascular stiffness with pulse wave velocity which is associated with cardiovascular outcomes in patients with CKD.
The active circulating form of vitamin D is 1,25 dihydroxy vitamin D (calcitriol). The level of calcitriol is regulated by the activity of the 1α hydroxylase enzyme located in the kidney. The 1α hydroxylase enzyme hydroxylate 25-hydroxy vitamin D at the 1-position. As kidney function declines the activity of 1α hydroxylase is reduced and thereby the circulating level of calcitriol is reduced. The reduced level of calcitriol, together with hypocalcaemia and hyperphosphatemia, leads to secondary hyperparathyroidism. Activated vitamin D is given to patients with hyperparathyroidism to try lowering PTH. In a randomized placebo-controlled trial with 36 patients with CKD G3-5 the intervention group were treated with active vitamin D, which resulted in a difference in BMD by +4.2% in the spine compared to controls after 18 months (P< 0.05). No clinical trials have aimed to explore the influence of targeting different levels of PTH and the influence on bone mineral density or bone fracture in patients with CKD.
Two randomized placebo-controlled trials aimed to address effect of 1 year of active vitamin D treatment on the left ventricular mass, a surrogate endpoint for development of heart failure. No difference between the treatment groups was found in any of the trials. Cohort studies in dialysis patients have found increased survival in patients treated with active vitamin D, but the result could be biased having the design in mind. One Japanese randomized controlled trial compared alfacalcidol with placebo in 976 patients on dialysis. Of importance, not all the included participants did have hyperparathyroidism. No difference was found in fatal and non-fatal cardiovascular events, additionally no difference was found in risk of fracture during the study. If this finding would have differed in patients with hyperparathyroidism or in patients with earlier stages of kidney disease and thereby preventable progression of vascular calcification, remains to be determined.
Treatment with active vitamin D, phosphate binders and calcimetics has been used for patients with CKD for decades. Recommendations regarding the appropriate dose and PTH target for different stages of CKD has varied during years and between guidelines, reflecting the lack of randomized clinical trials with clinical important end points.
In patients with CKD G3b-5, it is currently recommended to monitor the PTH every 3-6 month. As more than 50 % of the patients have elevated PTH already at CKD G3b, it is an everyday consideration for the clinician if the patients should be treated to reduce PTH. This is both time- and cost consuming. At present, there is no evidence to advise if secondary hyperparathyroidism should be treated in patients with CKD.
To improve knowledge about when secondary hyperparathyroidism should be treated, investigators want to conduct a randomized clinical trial with one group of patients being treated if PTH is elevated versus a second group of patients not being treated if PTH is elevated.
The investigators hypothesize that suppression of initially elevated PTH will improve BMD, arterial stiffness, muscle mass and muscle strength in patients with CKD.
Subjects will be recruited from the patient population in the outpatient clinic at the Department of Nephrology at Herlev and Gentofte Hospital, Herlev, Denmark.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
- Model description
- Intervention in both treatment groups is used to reach a target of PTH (different levels in different groups, no pre-defined treatment)
| Arm | Type | Receives |
|---|---|---|
| PTH intensive target | Experimental | Other: Treat to targetIntensive parathyroid hormone target (within interval of lower and upper normal limits = 2,0 - 8,5 µmol/L). In the intensive PTH target group, treatment will be initiated as soon as the PTH rise above the upper limit of normal. Participants in this group will receive treatment to lower PTH level (activated vitamin D, phosphate binder, native vitamin D and calcimetics). PTH will be measured as intact PTH with Atellica IM PTH assay at Herlev Hospital laboratory (normal range 2,0 - 8,5 µmol/L). |
| PTH liberal target | Experimental | Other: Treat to targetLiberal parathyroid hormone target (< 5 x upper normal limit = 42,5 µmol/L). In the liberal PTH target group, treatment will not be initiated until PTH rise above five times the upper limit of normal. This is expected to be a small part of the participants. The cut-off for the liberal PTH target (<5 x upper normal limit) was discussed in the national CKD-MBD group. It is chosen to allow the clinician initiate treatment if PTH reaches unusually high levels, no studies have focussed on PTH-targets before, consequently the cut-off is chosen as part of the pragmatic design. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- ≥50 years of age at screening
- CKD G4-5nonD (eGFR < 30 mL/min/1.73m2) based on local laboratory assessment of serum creatinine and eGFR estimated by the CKD-EPI formula)
- Plasma PTH > upper normal limit of local laboratory reference range (> 8,5µmol/L) and/or treated with active vitamin D (Alphacalcidol) or calcimetics (Cinacalcet) initially
- Written informed consent
Key exclusion criteria (2 listed)
- Patients who have received a kidney transplant
- Patients receiving treatment with specific anti-osteoporosis medication (denosumab/bisphosphonates) (because of the profound effect on calcium/phosphate fluxes and BMD)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Treat to targetParticipants will receive treatment from a "toolbox" depending on the situation to reach the PTH target. Available medication is mirroring what is used in the outpatient clinic setting already (native vitamin D, activated vitamin D, phosphate binders, calcimetics). | Other | PTH intensive target, PTH liberal target |
Primary outcome
Difference in percent change in bone mineral density (BMD) between the treatment groups.
Time frame: From baseline to final follow-up at 18 months
Measured with DEXA-scan
9 secondary outcomes
Difference in follow-up BMD between treatment groups
Time frame: From baseline to final follow-up at 18 months
Difference in follow-up arterial stiffness between the treatment groups
Time frame: From baseline to final follow-up at 18 months
Difference in follow-up muscle mass between the treatment groups
Time frame: From baseline to final follow-up at 18 months
Difference in follow-up hand grip strenght between the treatment groups
Time frame: From baseline to final follow-up at 18 months
Difference in follow-up 10 meter walk test between the treatment groups
Time frame: From baseline to final follow-up at 18 months
Difference in follow-up sit-to-stand test between the treatment groups
Time frame: From baseline to final follow-up at 18 months
Differences in bone histology between the treatment groups
Time frame: Labelling at baseline and repeated labelling and biopsy at 18 months
Differences in follow-up health-related quality of life between the treatment groups
Time frame: From baseline to final follow-up at 18 months
Differences in number of spinal fractures between the treatment groups
Time frame: From baseline to final follow-up at 18 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2026.
- Background: PubMed 7287505Rao SD, Matkovic V, Duncan H. Transiliac bone biopsy. Complications and diagnostic value. Henry Ford Hosp Med J. 1980;28(2-3):112-5. No abstract available.
- Background: PubMed 16376161Blake GM, Naeem M, Boutros M. Comparison of effective dose to children and adults from dual X-ray absorptiometry examinations. Bone. 2006 Jun;38(6):935-42. doi: 10.1016/j.bone.2005.11.007. Epub 2005 Dec 22.
- Background: PubMed 10028639Njeh CF, Fuerst T, Hans D, Blake GM, Genant HK. Radiation exposure in bone mineral density assessment. Appl Radiat Isot. 1999 Jan;50(1):215-36. doi: 10.1016/s0969-8043(98)00026-8.
- Backgroundhttps://www.fda.gov/media/175746/download
- Background: PubMed 17989106Frimodt-Moller M, Nielsen AH, Kamper AL, Strandgaard S. Reproducibility of pulse-wave analysis and pulse-wave velocity determination in chronic kidney disease. Nephrol Dial Transplant. 2008 Feb;23(2):594-600. doi: 10.1093/ndt/gfm470. Epub 2007 Nov 7.
- Background: PubMed 28892457Saag KG, Petersen J, Brandi ML, Karaplis AC, Lorentzon M, Thomas T, Maddox J, Fan M, Meisner PD, Grauer A. Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis. N Engl J Med. 2017 Oct 12;377(15):1417-1427. doi: 10.1056/NEJMoa1708322. Epub 2017 Sep 11.
- Background: PubMed 28993865Malluche HH, Monier-Faugere MC, Blomquist G, Davenport DL. Two-year cortical and trabecular bone loss in CKD-5D: biochemical and clinical predictors. Osteoporos Int. 2018 Jan;29(1):125-134. doi: 10.1007/s00198-017-4228-4. Epub 2017 Oct 9.
- Background: PubMed 40034486Kang DH, Park CH, Kim HW, Park JT, Han SH, Kim J, Jeong JC, Kim Y, Kim SW, Oh KH, Kang SW, Yoo TH. Kidney function and bone mineral density in chronic kidney disease patients. Clin Kidney J. 2024 Aug 13;17(9):sfae248. doi: 10.1093/ckj/sfae248. eCollection 2024 Sep.
- Background: PubMed 19644521Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl. 2009 Aug;(113):S1-130. doi: 10.1038/ki.2009.188.
- Background: PubMed 30675420Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group. KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl (2011). 2017 Jul;7(1):1-59. doi: 10.1016/j.kisu.2017.04.001. Epub 2017 Jun 21. No abstract available.
- Background: PubMed 30535217J-DAVID Investigators; Shoji T, Inaba M, Fukagawa M, Ando R, Emoto M, Fujii H, Fujimori A, Fukui M, Hase H, Hashimoto T, Hirakata H, Honda H, Hosoya T, Ikari Y, Inaguma D, Inoue T, Isaka Y, Iseki K, Ishimura E, Itami N, Ito C, Kakuta T, Kawai T, Kawanishi H, Kobayashi S, Kumagai J, Maekawa K, Masakane I, Minakuchi J, Mitsuiki K, Mizuguchi T, Morimoto S, Murohara T, Nakatani T, Negi S, Nishi S, Nishikawa M, Ogawa T, Ohta K, Ohtake T, Okamura M, Okuno S, Shigematsu T, Sugimoto T, Suzuki M, Tahara H, Takemoto Y, Tanaka K, Tominaga Y, Tsubakihara Y, Tsujimoto Y, Tsuruya K, Ueda S, Watanabe Y, Yamagata K, Yamakawa T, Yano S, Yokoyama K, Yorioka N, Yoshiyama M, Nishizawa Y. Effect of Oral Alfacalcidol on Clinical Outcomes in Patients Without Secondary Hyperparathyroidism Receiving Maintenance Hemodialysis: The J-DAVID Randomized Clinical Trial. JAMA. 2018 Dec 11;320(22):2325-2334. doi: 10.1001/jama.2018.17749.
- Background: PubMed 15728786Teng M, Wolf M, Ofsthun MN, Lazarus JM, Hernan MA, Camargo CA Jr, Thadhani R. Activated injectable vitamin D and hemodialysis survival: a historical cohort study. J Am Soc Nephrol. 2005 Apr;16(4):1115-25. doi: 10.1681/ASN.2004070573. Epub 2005 Feb 23.
- Individual participant dataSharing planned: No. We do not plan to share IPD as the trial will be conducted according to local legislation (Databeskyttelsesloven, Databeskyttelsesforordningen and Sundhedsloven), which does not allow sharing data.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ditte Hansen, Medical doctor, professor study director
Department of Nephrology, Herlev Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Treat to target in people with Chronic Kidney Disease Mineral and Bone Disorder, run by Herlev Hospital at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Freja S Hassager, Medical doctor (0045+22554707, freja.staehr.hassager.01@regionh.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in percent change in bone mineral density (BMD) between the treatment groups. (time frame: From baseline to final follow-up at 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07171216, which also lists 42 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2026.