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A Study on Spermatogenesis in Male Renal Transplant Recipients Receiving Valganciclovir (Valcyte®) Versus Untreated Matched Controls

Phase 4
Completed
Conditions
Cytomegalovirus Infections
Interventions
Registration Number
NCT01663740
Lead Sponsor
Hoffmann-La Roche
Brief Summary

This observational study will compare spermatogenesis in male adult renal transplant recipients receiving valganciclovir versus untreated matched controls. Data will be collected from each participant for up to 52 weeks post transplant.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
59
Inclusion Criteria
  • First renal transplant
  • Participant eligible to receive valganciclovir prophylaxis as determined by the treating physician in accordance with the local approved product prescribing information (Cohort A only) or the participant is not expected to require any valganciclovir prophylaxis (Cohort B only) post-transplant
  • Participant has no history of known infertility
  • Participant is able and willing to provide semen samples
  • Participant agrees to utilize a barrier contraceptive throughout the study or for at least 90 days after cessation of valganciclovir treatment
Exclusion Criteria
  • Prior ganciclovir or valganciclovir within 3 months of enrollment
  • Organ transplant other than kidney
  • Participant has received an investigational new drug in the 3 months prior to transplant
  • Participant hs received an alkylating agent or other medications known to affect fertility/spermatogenesis
  • Participant is unlikely to be available for follow-up for the entire duration of the study (up to 52 weeks)

Study & Design

Study Type
INTERVENTIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Cohort A: Partcipants who Received ValganciclovirValganciclovirParticipants with donor positive (D+)/recipient negative (R-) cytomegalovirus (CMV) serology, who receive valganciclovir prophylaxis according to the local prescribing information, will be observed for spermatogenesis up to 52 weeks post-transplant.
Primary Outcome Measures
NameTimeMethod
Change in Sperm Density From Baseline to the End of Treatment (EOT)Baseline, EOT (Week 28)

Sperm density was calculated based on the average of two semen samples. Change was calculated as the sperm density measured at post-baseline visit (EOT) minus (-) the sperm density measured at baseline for each participant. A negative change from baseline indicated a lower sperm density (worsening).

Secondary Outcome Measures
NameTimeMethod
Change in LH Level From EOT to End of FUEOT (Week 28), end of FU (Week 52)

LH level was calculated based on the average of two samples. Change was calculated as the LH level measured at FU - the LH level measured at EOT for each participant. A negative change from EOT indicated a lower LH level.

Percentage of Participants With Improved TUNEL Score From EOT to End of FUEOT (Week 28), end of FU (Week 52)

Sperm DNA fragmentation change (chromatin damage) was evaluated based on TUNEL score. Participants who had a lower TUNEL score compared to the previous time point were considered as improved.

Percentage of Participants With Improved Sperm Density From EOT to End of FUEOT (Week 28), end of FU (Week 52)

Participants who had higher sperm density compared with the previous visit were considered as improved.

Change in Sperm Morphology Evaluated as Percentage of Normal Sperm Cells From EOT to End of FUEOT (Week 28), end of FU (Week 52)

Sperm morphology was evaluated based on the average of two semen samples. Change was calculated as the sperm morphology measured at FU - the sperm morphology measured at EOT for each participant. A positive change from EOT indicated an improved sperm morphology.

Change in FSH Level From EOT to End of FUEOT (Week 28), end of FU (Week 52)

FSH level was calculated based on the average of two samples. Change was calculated as the FSH level measured at FU - the FSH level measured at EOT for each participant. A negative change from EOT indicated a lower FSH level.

Percentage of Participants With Abnormal Sperm Density (<20 Mil/mL) From EOT to End of FUEOT (Week 28), end of FU (Week 52)

Abnormal sperm density was considered as sperm density \<20 mil/mL. Change in abnormal to abnormal sperm density and normal to abnormal sperm density from EOT to end of FU was reported.

Change in Seminal Volume From Baseline to EOT and End of FUBaseline, EOT (Week 28), end of FU (Week 52)

Seminal volume was calculated based on the average of two semen samples. Change was calculated as the seminal volume measured at post-baseline visit (EOT and FU) - the seminal volume measured at baseline for each participant. A negative change from baseline indicated a lower seminal volume (worsening).

Change in Prolactin Level From Baseline to EOT and End of FUBaseline, EOT (Week 28), end of FU (Week 52)

Prolactin level was calculated based on the average of two samples. Change was calculated as the prolactin level measured at post-baseline visit (EOT and FU) - the prolactin level measured at baseline for each participant. A negative change from baseline indicated a lower prolactin level.

Change in TUNEL Score From EOT to End of FUEOT (Week 28), end of FU (Week 52)

Sperm DNA fragmentation change (chromatin damage) was evaluated based on TUNEL score. Change was calculated as the TUNEL score measured at FU minus the TUNEL score measured at EOT for each participant. A negative change from EOT indicated a lower TUNEL score. TUNEL score represents percentage of sperm with fragmented DNA; total score ranged from 0% to 100%, higher score represents more fragmentation.

Change in Seminal Volume From EOT to End FUEOT (Week 28), end of FU (Week 52)

Seminal volume was calculated based on the average of two semen samples. Change was calculated as the seminal volume measured at FU - the seminal volume measured at EOT for each participant. A negative change from EOT indicated a lower seminal volume (worsening).

Change in Sperm Density From EOT to End of FUEOT (Week 28), end of FU (Week 52)

Sperm density was calculated based on the average of two semen samples. Change was calculated as the sperm density measured at FU - the sperm density measured at EOT for each participant. A negative change from EOT indicated a lower sperm density (worsening).

Change in Total Motility of Sperm From EOT to End of FUEOT (Week 28), end of FU (Week 52)

Sperm motility was calculated based on the average of two semen samples. Percent was determined by the calculation of motile sperm/total sperm count. Change was calculated as the sperm motility measured at FU - the sperm motility measured at EOT for each participant. A negative change from EOT indicated a lower sperm motility (worsening).

Change in Sperm Morphology Evaluated as Percentage of Normal Sperm Cells From Baseline to EOT and End of FUBaseline, EOT (Week 28), end of FU (Week 52)

Sperm morphology was evaluated based on the average of two semen samples. Change was calculated as the sperm morphology measured at post-baseline visit (EOT and FU) - the sperm morphology measured at baseline for each participant. A positive change from baseline indicated an improved sperm morphology.

Change in Total Testosterone Level From EOT to End of FUEOT (Week 28), end of FU (Week 52)

Testosterone level was calculated based on the average of two samples. Change was calculated as the testosterone level measured at FU - the testosterone level measured at EOT for each participant. A negative change from EOT indicated a lower testosterone level.

Change in FSH Level From Baseline to EOT and End of FUBaseline, EOT (Week 28), end of FU (Week 52)

FSH level was calculated based on the average of two samples. Change was calculated as the FSH level measured at post-baseline visit (EOT and FU) - the FSH level measured at baseline for each participant. A negative change from baseline indicated a lower FSH level.

Change in Prolactin Level From EOT to End of FUEOT (Week 28), end of FU (Week 52)

Prolactin level was calculated based on the average of two samples. Change was calculated as the prolactin level measured at FU - the prolactin level measured at EOT for each participant. A negative change from EOT indicated a lower prolactin level.

Change in Inhibin B Level From Baseline to EOT and End of FUBaseline, EOT (Week 28), end of FU (Week 52)

Inhibin B level was calculated based on the average of two samples. Change was calculated as the inhibin B level measured at post-baseline visit (EOT and FU) - the inhibin B level measured at baseline for each participant. A negative change from baseline indicated a lower inhibin B level.

Change in Terminal Uridine Nick-End Labeling (TUNEL) Score From Baseline to EOT and End of Follow-up (FU)Baseline, EOT (Week 28), end of FU (Week 52)

Sperm DNA fragmentation change (chromatin damage) was evaluated based on TUNEL score. Change was calculated as the TUNEL score measured at post-baseline visit (EOT and FU) minus the TUNEL score measured at baseline for each participant. A negative change from baseline indicated a lower TUNEL score. TUNEL score represents percentage of sperm with fragmented DNA; total score ranged from 0 percent (%) to 100%, higher score represents more fragmentation.

Change in Sperm Density From Baseline to End of FUBaseline, end of FU (Week 52)

Sperm density was calculated based on the average of two semen samples. Change was calculated as the sperm density measured at post-baseline visit (FU) - the sperm density measured at baseline for each participant. A negative change from baseline indicated a lower sperm density (worsening).

Change in Total Motility of Sperm From Baseline to EOT and End of FUBaseline, EOT (Week 28), end of FU (Week 52)

Sperm motility was calculated based on the average of two semen samples. Percent was determined by the calculation of motile sperm/total sperm count. Change was calculated as the sperm motility measured at post-baseline visit (EOT and FU) - the sperm motility measured at baseline for each participant. A negative change from baseline indicated a lower sperm motility (worsening).

Change in Total Testosterone Level From Baseline to EOT and End of FUBaseline, EOT (Week 28), end of FU (Week 52)

Testosterone level was calculated based on the average of two samples. Change was calculated as the testosterone level measured at post-baseline visit (EOT and FU) - the testosterone level measured at baseline for each participant. A negative change from baseline indicated a lower testosterone level.

Change in LH Level From Baseline to EOT and End of FUBaseline, EOT (Week 28), end of FU (Week 52)

LH level was calculated based on the average of two samples. Change was calculated as the LH level measured at post-baseline visit (EOT and FU) - the LH level measured at baseline for each participant. A negative change from baseline indicated a lower LH level.

Percentage of Participants With Abnormal Sperm Density (<20 Mil/mL) From Baseline to EOT and End of FUBaseline, EOT (Week 28), end of FU (Week 52)

Abnormal sperm density was considered as sperm density less than (\<) 20 mil/mL. Change in abnormal to abnormal sperm density and normal to abnormal sperm density from baseline to EOT and end of FU was reported.

Change in Inhibin B Level From EOT to End of FUEOT (Week 28), end of FU (Week 52)

Inhibin B level was calculated based on the average of two samples. Change was calculated as the inhibin B level measured at FU - the inhibin B level measured at EOT for each participant. A negative change from EOT indicated a lower inhibin B level.

Percentage of Participants With Improved TUNEL Score From Baseline to EOT and End of FUBaseline, EOT (Week 28), end of FU (Week 52)

Sperm DNA fragmentation change (chromatin damage) was evaluated based on TUNEL score. Participants who had a lower TUNEL score compared to the previous time point were considered as improved.

Percentage of Participants With Improved Sperm Density From Baseline to EOT and End of FUBaseline, EOT (Week 28), end of FU (Week 52)

Participants who had higher sperm density compared with the previous visit were considered as improved.

Trial Locations

Locations (19)

Tufts Medical Center

🇺🇸

Boston, Massachusetts, United States

University of Minnesota

🇺🇸

Minneapolis, Minnesota, United States

University of California at San Francisco

🇺🇸

San Francisco, California, United States

National Institute of Transplantation

🇺🇸

Los Angeles, California, United States

University of California Los Angeles (UCLA)

🇺🇸

Los Angeles, California, United States

Medical College of Georgia

🇺🇸

Augusta, Georgia, United States

Western New England Renal & Transplant Associates, P.C.

🇺🇸

Springfield, Massachusetts, United States

Mayo Clinic Rochester

🇺🇸

Rochester, Minnesota, United States

Albany Medical Cancer Center

🇺🇸

Albany, New York, United States

University at Buffalo

🇺🇸

Buffalo, New York, United States

Stony Brook University Hospital

🇺🇸

Stony Brook, New York, United States

Drexel University Department of Nephrology

🇺🇸

Philadelphia, Pennsylvania, United States

Methodist Healthcare System of San Antonio

🇺🇸

San Antonio, Texas, United States

Hospital Miguel Hidalgo

🇲🇽

Aguascalientes, Mexico

Instituto Mexicano de Trasplantes

🇲🇽

Cuernavaca, Mexico

Hospital Central Dr. Ignacio Morones Prieto

🇲🇽

San Luis Potosi, Mexico

Oregan Health & Science Univ

🇺🇸

Portland, Oregon, United States

Washington Hospital Center

🇺🇸

Washington, District of Columbia, United States

Rhode Island Hospital

🇺🇸

Providence, Rhode Island, United States

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