A Phase 1/2 interventional study of Rapamune in Polycystic Kidney Diseases, sponsored by The Cleveland Clinic. Completed at 1 site in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2015-04-06.
Sponsored by The Cleveland Clinic · Phase 1/2, Interventional, and Treatment
This study is a prospective, randomized, open-label, pilot clinical trial designed to compare the effects of an agent that has antiproliferative (1,2), antiangiogenesis (3),and tumor-progression blocking capabilities (4), namely, rapamycin (Rapamune®), in the treatment of autosomal-dominant polycystic kidney disease (ADPKD).
Up to this time, only generic renal disease treatments for ADPKD have been in use, such as the treatment of hypertension, urinary tract infections, renal stones, renal call carcinomas, and replacement therapy with dialysis and/or renal transplantation. The fundamental aberrations in ADPKD are proliferation of cyst-forming tubuloepithelial cells, secretion of cytokine-rich fluid into those cysts, and progressive cyst expansion and release of inflammatory mediators that injure surrounding normal renal tissue. Consequently, therapy directed specifically at blocking the proliferation of tubuloepithelial cells and their tendency to malignant transformation, as well as impeding their blood supply, should have obvious merit.
General Procedures:
In Group I participants will have an iothalamate glomerular filtration rate (GFR) equal to or greater than 60 ml/min/1.73 m2, and in Group II participants will have a GFR less than 25-59 ml/min/1.73 m2. Both males and females with ADPKD who volunteer and qualify, will be randomly and prospectively assigned to treatment with rapamycin at either a high or low trough blood level or to standard care (each 1/3 of enrolled patients) for one year. The two treatment groups will receive rapamycin doses aimed at maintaining the 20- to 24-hour trough blood levels at either 2 to 5 ng/mL (low-dose), or greater than 5 to 8 ng/mL (high-dose). These trough levels are in the lower range of levels used when treating renal transplant recipients in whom trough levels are typically maintained between 5 and 15 ng/mL.
This study is a prospective, randomized,open label, pilot clinical trial designed to compare the effects of an agent that has antiproliferative (1,2), antiangiogenesis (3),and tumor-progression blocking capabilities (4), namely, rapamycin (Rapamune®), in the treatment of autosomal-dominant polycystic kidney disease (ADPKD).
Up to this time, only generic renal disease treatments for ADPKD have been in use, such as the treatment of hypertension, urinary tract infections, renal stones, renal call carcinomas, and replacement therapy with dialysis and/or renal transplantation. The fundamental aberrations in ADPKD are proliferation of cyst-forming tubuloepithelial cells, secretion of cytokine-rich fluid into those cysts, and progressive cyst expansion and release of inflammatory mediators that injure surrounding normal renal tissue. Consequently, therapy directed specifically at blocking the proliferation of tubuloepithelial cells and their tendency to malignant transformation, as well as impeding their blood supply, should have obvious merit.
General Procedures:
In Group I participants will have an iothalamate glomerular filtration rate (GFR) equal to or greater than 60 ml/min/1.73 m2, and in Group II participants will have a GFR less than 25-59 ml/min/1.73 m2. Both males and females with ADPKD who volunteer and qualify, will be randomly and prospectively assigned to treatment with rapamycin at either a high or low trough blood level or to standard care (each 1/3 of enrolled patients) for one year. The two treatment groups will receive rapamycin doses aimed at maintaining the 20- to 24-hour trough blood levels at either 2 to 5 ng/mL (low-dose), or greater than 5 to 8 ng/mL (high-dose). These trough levels are in the lower range of levels used when treating renal transplant recipients in whom trough levels are typically maintained between 5 and 15 ng/mL.
3,840 studies on the registry are indexed under Kidney Diseases; 500 are open to participants now.
This study's enrollment of 30 is below the median of 70 across 2,640 interventional studies indexed under Kidney Diseases.
Browse Kidney Diseases studies →The Cleveland Clinic is the lead sponsor of 818 studies on the registry; 118 are open to participants now.
Of its 89 completed or terminated interventional studies of FDA-regulated products, 72 (81%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Arm 1 Rapamune dose 2-6mg aimed at maintaining trough levels 5-8 ng/ml
Drug: Rapamune
Arm 2 Rapamune dose 2-6 mg aimed at maintaining trough levels of 2-5ng/ml
Drug: Rapamune
Standard Care
Group 1- doses of Rapamune aimed at maintaining trough levels 5-8ng/ml Group 2 - doses of Rapamune aimed at maintaining trough levels 2-5ng/ml Group 3- Standard Care
Also known as: Rapamycin
Change in GFR From Baseline to 12 Months
GFR (glomerular filtration rate) was measured by iothalamate. GFR is a key indicator of renal function.
Time frame: From baseline to 12 months
Change in Total Kidney Volume as Measured by 3D-CT From Baseline to 12 Months
Total kidney volume measured by CT from baseline to 12 months
Time frame: From baseline to 12 months
| Milestone | Standard Rapamycin Dose (STD) | Low Dose Rapamycin (LD) | Standard Care |
|---|---|---|---|
| Started | 10 | 10 | 10 |
| Completed | 8 | 9 | 9 |
| Not completed | 2 | 1 | 1 |
| Withdrew: Missed 12 month visit | 0 | 0 | 1 |
| Withdrew: Ae: pulmonary embolus | 0 | 1 | 0 |
| Withdrew: Ae: nephrotic-range proteinuruia | 1 | 0 | 0 |
| Withdrew: Ae: pneumonia | 1 | 0 | 0 |
GFR (glomerular filtration rate) was measured by iothalamate. GFR is a key indicator of renal function.
| ml/min/1.73m^2 | Standard Rapamycin Dose (STD) | Low Dose Rapamycin (LD) | Standard Care |
|---|---|---|---|
| Baseline iGFR | 72.8 ± 25.7 | 70.3 ± 27.0 | 73.1 ± 20.3 |
| 12 month iGFR | 74.4 ± 34.4 | 78.0 ± 35.0 | 61.9 ± 15.6 |
| Change in iGFR | 1.6 ± 12.1 | 7.7 ± 12.5 | -11.2 ± 9.1 |
Total kidney volume measured by CT from baseline to 12 months
| ml | Standard Rapamycin Dose (STD) | Low Dose Rapamycin (LD) | Standard Care |
|---|---|---|---|
| Baseline TKV | 1454.1 ± 801.5 | 1919.1 ± 903.6 | 1907.1 ± 1126.8 |
| 12 month TKV | 1537 ± 864.3 | 2115.8 ± 1035.0 | 2059.8 ± 1236.0 |
| Change in TKV | 82.9 ± 111.3 | 197.7 ± 201.2 | 152.7 ± 129.4 |
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Standard Rapamycin Dose (STD) | — | 2/10 (20%) | 10/10 (100%) |
| Low Dose Rapamycin (LD) | — | 1/10 (10%) | 6/10 (60%) |
| Standard Care | — | 1/10 (10%) | 8/10 (80%) |
| Event | Standard Rapamycin Dose (STD) | Low Dose Rapamycin (LD) | Standard Care |
|---|---|---|---|
| pulmonary embolusRespiratory, thoracic and mediastinal disorders | 0/10 | 1/10 | 0/10 |
| nephrotic range proteinuriaRenal and urinary disorders | 1/10 | 0/10 | 0/10 |
| Decrease visual acuityEye disorders | 1/10 | 0/10 | 0/10 |
| HypoglycemiaMetabolism and nutrition disorders | 0/10 | 0/10 | 1/10 |
| Event | Standard Rapamycin Dose (STD) | Low Dose Rapamycin (LD) | Standard Care |
|---|---|---|---|
| Oral ulcerationsImmune system disorders | 6/10 | 2/10 | 0/10 |
| Nonserious infectionsInfections and infestations | 6/10 | 2/10 | 5/10 |
| Miscellaneous/otherGeneral disorders | 4/10 | 2/10 | 5/10 |
| Gastrointestinal symptomsGastrointestinal disorders | 3/10 | 1/10 | 4/10 |
| EdemaBlood and lymphatic system disorders | 1/10 | 0/10 | 2/10 |
| DermatitisSkin and subcutaneous tissue disorders | 0/10 | 2/10 | 0/10 |
| Age, Continuous(years) | Standard Rapamycin Dose (STD) | Low Dose Rapamycin (LD) | Standard Care | Total |
|---|---|---|---|---|
| Mean | 53.2 ± 15.0 | 44.9 ± 8.6 | 49.4 ± 11.0 | 49.3 ± 12.0 |
| Sex: Female, Male(Participants) | Standard Rapamycin Dose (STD) | Low Dose Rapamycin (LD) | Standard Care | Total |
|---|---|---|---|---|
| Female | 5 | 5 | 3 | 13 |
| Male | 5 | 5 | 7 | 17 |
| Race (NIH/OMB)(Participants) | Standard Rapamycin Dose (STD) | Low Dose Rapamycin (LD) | Standard Care | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 1 | 1 |
| White | 10 | 10 | 9 | 29 |
| More than one race | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| Region of Enrollment(participants) | Standard Rapamycin Dose (STD) | Low Dose Rapamycin (LD) | Standard Care | Total |
|---|---|---|---|---|
| United States | 10 | 10 | 10 | 30 |
| Baseline characteristics and risk factors(participants) | Standard Rapamycin Dose (STD) | Low Dose Rapamycin (LD) | Standard Care | Total |
|---|---|---|---|---|
| Hypertension | 3 | 3 | 5 | 11 |
| Family history of ESRD | 4 | 8 | 7 | 19 |
| Initial iGFR 25-59 ml/min per 1.73 m^2 | 3 | 4 | 2 | 9 |
| Initial TKV>1500ml | 6 | 7 | 6 | 19 |
| Initial height-adjusted TKV>=600ml/m | 6 | 8 | 6 | 20 |
This study is completed, as verified in Mar 2014. You cannot join it, but the record below documents what was studied.
Get 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.
The Cleveland Clinic