Chronic Kidney DiseasePhase 2COMBINENCT02258074
The COMBINE Study: The CKD Optimal Management With BInders and NicotinamidE
A Phase 2 study testing Nicotinamide and Lanthanum Carbonate in people with Chronic Kidney Disease, run by The Cleveland Clinic at 7 sites in United States.
Trial summary
The COMBINE clinical trial is a pilot study evaluating the effects of nicotinamide and lanthanum carbonate on serum phosphate and fibroblast growth factor 23 (FGF23) in patients with Chronic Kidney Disease (CKD) stages 3-4. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Chronic Kidney Disease
- What is being tested?
- Nicotinamide and Lanthanum Carbonate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 205 participants
- Where
- 7 sitesUnited States
- Study dates
- Mar 2015to Sep 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with estimated glomerular filtration rate (eGFR) 20-45 ml/min/1.73m2
- Age 18-85 years
- Serum phosphate ≥ 2.8 mg/dL
- Platelet count ≥ 125,000/mm3
- Able to provide consent
- Able to travel to study visits
- Able to eat at least two meals a day
- In the opinion of the site investigator, willing and able to follow the study treatment regimen and comply with the site investigator's recommendations.
Who cannot join
- History of allergic reaction to nicotinamide, niacin (excluding flushing), multivitamin preparations, or lanthanum carbonate
- Liver disease, defined as known cirrhosis by imaging or physician diagnosis, documented alcohol use > 14 drinks/week, or aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, or total bilirubin concentrations > 2 times the upper limit of the local laboratory reference range
- Creatine kinase (CK) concentrations > 2 times the upper limit of the local laboratory reference range
- Major hemorrhagic event within the past six months requiring in-patient admission
- Blood or platelet transfusion within the past six months
- Secondary hyperparathyroidism (PTH > 5 times the upper limit of normal range for the laboratory) or currently taking cinacalcet (Sensipar)
Show all 19Show fewer
- Current, clinically significant malabsorption, as determined at the discretion of the site investigator
- Anemia (screening Hg < 9.0 g/dl)
- Serum albumin < 2.5 mg/dl
- Anticipated initiation of dialysis or kidney transplantation within 12 months as assessed by and at the discretion of the site investigator.
- Use of immunosuppressive medications (stable oral steroids ≤ 10 mg of prednisone/day or inhaled steroids are exempted)
- In the opinion of the site investigator, active abuse of alcohol or drugs
- Recent (within the last 14 days) initiation or change in dose of treatment with 1,25 (OH)2 vitamin D or active vitamin D analogues (paricalcitol or hectorol). Patients on stable doses of these agents initiated more than 14 days prior to screening are eligible to participate.
- Current or recent treatment (within the last 14 days) with phosphate binder or niacin/nicotinamide > 100 mg/day
- Current participation in another clinical trial or other interventional research
- Currently taking investigational drugs
- Institutionalized individuals, including prisoners and nursing home residents
- Malignancy requiring therapy within 2 years (basal or squamous cell skin carcinoma and localized prostate cancer are exempted)
- -
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
NorthShore University Health System
Chicago, Illinois, 60201
Northwestern University
Chicago, Illinois, 60611
Denver Nephrology Research
Denver, Colorado, 80230
University of Utah
Salt Lake City, Utah, 84112
Utah VA
Salt Lake City, Utah, 84112
University of California at San Diego
San Diego, California, 92161
George Washington University
Washington D.C., District of Columbia, 20037
About this study
The COMBINE clinical trial is a pilot study evaluating the effects of nicotinamide and lanthanum carbonate on serum phosphate and fibroblast growth factor 23 (FGF23) in patients with Chronic Kidney Disease (CKD) stages 3-4.
- Conditions
- Chronic Kidney Disease
- Being tested
- Nicotinamide, Lanthanum Carbonate, Placebo (for Nicotinamide), Placebo (for lanthanum carbonate)
- Medical subject headings
- Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NicotinamideDrug
Lanthanum CarbonateDrug
Placebo (for Nicotinamide)Drug
Sugar pill manufactured to mimic Nicotinamide 750 mg capsule
Placebo (for lanthanum carbonate)Drug
Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule
| Study group | Role | What they receive |
|---|---|---|
| Lanthanum carbonate + nicotinamide | Experimental | One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months. Receives: Drug: Nicotinamide; Drug: Lanthanum Carbonate |
| Lanthanum carbonate + nicotinamide placebo | Placebo comparator | Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months. One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Receives: Drug: Lanthanum Carbonate; Drug: Placebo (for Nicotinamide) |
| Lanthanum carbonate placebo and nicotinamide | Active comparator | One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months. Receives: Drug: Nicotinamide; Drug: Placebo (for lanthanum carbonate) |
| Lanthanum carbonate placebo and nicotinamide placebo | Placebo comparator | One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months. Receives: Drug: Placebo (for Nicotinamide); Drug: Placebo (for lanthanum carbonate) |
What is being measured
The primary outcome is the main question the study is designed to answer.
FGF23
Change from baseline to 12 months in FGF23 level.
Measured: Baseline to 12 months
Serum Phosphate (mg/dl)
Change from Baseline to 12 months in serum phosphate level
Measured: Baseline to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2014 (estimated)
- Study startMar 2015
- Primary completionNov 2018
- Study completionSep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Chronic Kidney DiseaseStudies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 205 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jennifer Gassman, PhD, The Cleveland Clinic
- Investigators
- Michael F. Flessner, MD, PhD, Study director, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)John W. Kusek, PhD, Study director, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Jennifer J Gassman, Ph.D., Principal investigator, Data Coordinating Center, Cleveland ClinicLinda F Fried, MD, Study chair, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02258074
- Sponsor's protocol ID
- DK099877-C
- Other IDs
- U01DK099877
- Acronym
- COMBINE
- Status last verified
- Jul 2021
- First submitted
- 28 Jul 2014
- Last updated
- 2 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The study data will be archived in the NIDDK Data Repository.
Publications
Isakova T, Ix JH, Sprague SM, Raphael KL, Fried L, Gassman JJ, Raj D, Cheung AK, Kusek JW, Flessner MF, Wolf M, Block GA. Rationale and Approaches to Phosphate and Fibroblast Growth Factor 23 Reduction in CKD. J Am Soc Nephrol. 2015 Oct;26(10):2328-39. doi: 10.1681/ASN.2015020117. Epub 2015 May 12.
PubMed 25967123Ix JH, Isakova T, Larive B, Raphael KL, Raj DS, Cheung AK, Sprague SM, Fried LF, Gassman JJ, Middleton JP, Flessner MF, Block GA, Wolf M. Effects of Nicotinamide and Lanthanum Carbonate on Serum Phosphate and Fibroblast Growth Factor-23 in CKD: The COMBINE Trial. J Am Soc Nephrol. 2019 Jun;30(6):1096-1108. doi: 10.1681/ASN.2018101058. Epub 2019 May 13.
PubMed 31085679Natale P, Green SC, Ruospo M, Craig JC, Vecchio M, Elder GJ, Strippoli GF. Phosphate binders for preventing and treating chronic kidney disease-mineral and bone disorder (CKD-MBD). Cochrane Database Syst Rev. 2025 Jun 27;6(6):CD006023. doi: 10.1002/14651858.CD006023.pub4.
PubMed 40576086Trujillo J, Alotaibi M, Seif N, Cai X, Larive B, Gassman J, Raphael KL, Cheung AK, Raj DS, Fried LF, Sprague SM, Block G, Chonchol M, Middleton JP, Wolf M, Ix JH, Prasad P, Isakova T, Srivastava A. Associations of Kidney Functional Magnetic Resonance Imaging Biomarkers with Markers of Inflammation in Individuals with CKD. Kidney360. 2024 May 1;5(5):681-689. doi: 10.34067/KID.0000000000000437. Epub 2024 Apr 4.
PubMed 38570905Srivastava A, Cai X, Lee J, Li W, Larive B, Kendrick C, Gassman JJ, Middleton JP, Carr J, Raphael KL, Cheung AK, Raj DS, Chonchol MB, Fried LF, Block GA, Sprague SM, Wolf M, Ix JH, Prasad PV, Isakova T. Kidney Functional Magnetic Resonance Imaging and Change in eGFR in Individuals with CKD. Clin J Am Soc Nephrol. 2020 Jun 8;15(6):776-783. doi: 10.2215/CJN.13201019. Epub 2020 Apr 28.
PubMed 32345747
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The COMBINE Study: The CKD Optimal Management With BInders and NicotinamidE
- ClinicalTrials.gov ID
- NCT02258074
- Acronym / sponsor ID
- COMBINE / DK099877-C
- Conditions
- Chronic Kidney Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 205 participants (actual)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Mar 2015 (actual)
- Primary completion
- Nov 2018 (actual)
- Study completion
- Sep 2019 (actual)
- First posted
- 7 Oct 2014 (estimated)
- Results
- Posted 30 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The COMBINE clinical trial is a pilot study evaluating the effects of nicotinamide and lanthanum carbonate on serum phosphate and fibroblast growth factor 23 (FGF23) in patients with Chronic Kidney Disease (CKD) stages 3-4.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Lanthanum carbonate + nicotinamide | Experimental | Drug: Nicotinamide, Drug: Lanthanum CarbonateOne nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months. |
| Lanthanum carbonate + nicotinamide placebo | Placebo comparator | Drug: Lanthanum Carbonate, Drug: Placebo (for Nicotinamide)Two lanthanum carbonate 500 mg capsules by mouth with each meal (3000 mg) for 12 months. One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months. |
| Lanthanum carbonate placebo and nicotinamide | Active comparator | Drug: Nicotinamide, Drug: Placebo (for lanthanum carbonate)One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months. |
| Lanthanum carbonate placebo and nicotinamide placebo | Placebo comparator | Drug: Placebo (for Nicotinamide), Drug: Placebo (for lanthanum carbonate)One Placebo (for nicotinamide) 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients with estimated glomerular filtration rate (eGFR) 20-45 ml/min/1.73m2
- Age 18-85 years
- Serum phosphate ≥ 2.8 mg/dL
- Platelet count ≥ 125,000/mm3
- Able to provide consent
Key exclusion criteria (19 listed)
- History of allergic reaction to nicotinamide, niacin (excluding flushing), multivitamin preparations, or lanthanum carbonate
- Liver disease, defined as known cirrhosis by imaging or physician diagnosis, documented alcohol use > 14 drinks/week, or aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, or total bilirubin concentrations > 2 times the upper limit of the local laboratory reference range
- Creatine kinase (CK) concentrations > 2 times the upper limit of the local laboratory reference range
- Major hemorrhagic event within the past six months requiring in-patient admission
- Blood or platelet transfusion within the past six months
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 |
|---|---|---|
| Nicotinamide | Drug | Lanthanum carbonate + nicotinamide, Lanthanum carbonate placebo and nicotinamide |
| Lanthanum Carbonate | Drug | Lanthanum carbonate + nicotinamide, Lanthanum carbonate + nicotinamide placebo |
| Placebo (for Nicotinamide)Sugar pill manufactured to mimic Nicotinamide 750 mg capsule | Drug | Lanthanum carbonate + nicotinamide placebo, Lanthanum carbonate placebo and nicotinamide placebo |
| Placebo (for lanthanum carbonate)Sugar pill manufactured to mimic Lanthanum Carbonate 500 mg capsule | Drug | Lanthanum carbonate placebo and nicotinamide, Lanthanum carbonate placebo and nicotinamide placebo |
Primary outcome
FGF23
Time frame: Baseline to 12 months
Change from baseline to 12 months in FGF23 level.
Serum Phosphate (mg/dl)
Time frame: Baseline to 12 months
Change from Baseline to 12 months in serum phosphate level
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25967123Isakova T, Ix JH, Sprague SM, Raphael KL, Fried L, Gassman JJ, Raj D, Cheung AK, Kusek JW, Flessner MF, Wolf M, Block GA. Rationale and Approaches to Phosphate and Fibroblast Growth Factor 23 Reduction in CKD. J Am Soc Nephrol. 2015 Oct;26(10):2328-39. doi: 10.1681/ASN.2015020117. Epub 2015 May 12.
- Results publication: PubMed 31085679Ix JH, Isakova T, Larive B, Raphael KL, Raj DS, Cheung AK, Sprague SM, Fried LF, Gassman JJ, Middleton JP, Flessner MF, Block GA, Wolf M. Effects of Nicotinamide and Lanthanum Carbonate on Serum Phosphate and Fibroblast Growth Factor-23 in CKD: The COMBINE Trial. J Am Soc Nephrol. 2019 Jun;30(6):1096-1108. doi: 10.1681/ASN.2018101058. Epub 2019 May 13.
- Derived from this study: PubMed 40576086Natale P, Green SC, Ruospo M, Craig JC, Vecchio M, Elder GJ, Strippoli GF. Phosphate binders for preventing and treating chronic kidney disease-mineral and bone disorder (CKD-MBD). Cochrane Database Syst Rev. 2025 Jun 27;6(6):CD006023. doi: 10.1002/14651858.CD006023.pub4.
- Derived from this study: PubMed 38570905Trujillo J, Alotaibi M, Seif N, Cai X, Larive B, Gassman J, Raphael KL, Cheung AK, Raj DS, Fried LF, Sprague SM, Block G, Chonchol M, Middleton JP, Wolf M, Ix JH, Prasad P, Isakova T, Srivastava A. Associations of Kidney Functional Magnetic Resonance Imaging Biomarkers with Markers of Inflammation in Individuals with CKD. Kidney360. 2024 May 1;5(5):681-689. doi: 10.34067/KID.0000000000000437. Epub 2024 Apr 4.
- Derived from this study: PubMed 32345747Srivastava A, Cai X, Lee J, Li W, Larive B, Kendrick C, Gassman JJ, Middleton JP, Carr J, Raphael KL, Cheung AK, Raj DS, Chonchol MB, Fried LF, Block GA, Sprague SM, Wolf M, Ix JH, Prasad PV, Isakova T. Kidney Functional Magnetic Resonance Imaging and Change in eGFR in Individuals with CKD. Clin J Am Soc Nephrol. 2020 Jun 8;15(6):776-783. doi: 10.2215/CJN.13201019. Epub 2020 Apr 28.
- Individual participant dataSharing planned: Yes. The study data will be archived in the NIDDK Data Repository.
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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. This study is not recruiting at the moment.
Michael F. Flessner, MD, PhD study director
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
John W. Kusek, PhD study director
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Jennifer J Gassman, Ph.D. principal investigator
Data Coordinating Center, Cleveland Clinic
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nicotinamide and Lanthanum Carbonate in people with Chronic Kidney Disease, run by The Cleveland Clinic at 7 sites in United States.
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 8 inclusion and 19 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: finished, as of the sponsor's last update on 2 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
FGF23 (time frame: Baseline to 12 months). The study lists 2 primary outcomes in all. 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 NCT02258074, which also lists 5 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 2 Aug 2021.