Trial Outcomes & Findings for The Effect and Safety of Lisinopril in Non-hypertensive Men With Infertility From Low Sperm Count (NCT NCT01409837)
NCT ID: NCT01409837
Last Updated: 2013-11-25
Results Overview
The seminal fluid characteristics were assessed twice before the entry of each patient and both at least two-weeks apart. The two values were averaged and recorded as baseline for week 0 while subsequent changes from the baseline were monitored during each of the scheduled visits at weeks 6, 12, 24, 48, 96, 102, 114, 138, 186 and 282. The two groups swopped treatments at the 96th week. The number of pregnancies achieved was also documented throughout the study period.
COMPLETED
PHASE2
33 participants
Week 96.
2013-11-25
Participant Flow
As per protocol the recruitment of patients took place from March 1998 to September 2001 while the actual investigation took place from January 2002 to December 2006.
During the recruitment period a total of 131 male patients being treated for low sperm count of unknown cause volunteered to participate. They were screened based on the criteria for eligibility as per protocol. Only 33 (25.2%) satisfied the inclusion criteria and were randomized such that 16 were in group A while 17 were in group B.
Participant milestones
| Measure |
Group B (Lisinopril First, Then Placebo)
Started with Lisinopril 2.5 mg taken once a day. Then crossed over to Sugar Pill taken also once a day. The Lisinopril and the Sugar Pill were made indistinguishable in appearance.
|
Group A (Placebo First, Then Lisinopril)
Started with Sugar Pill taken once daily. Then crossed over to Lisinopril 2.5 mg taken once a day.
|
|---|---|---|
|
Overall Study
STARTED
|
17
|
16
|
|
Overall Study
6th Week
|
17
|
16
|
|
Overall Study
12th Week
|
16
|
16
|
|
Overall Study
24th Week
|
16
|
15
|
|
Overall Study
48th Week
|
15
|
15
|
|
Overall Study
96th Week
|
15
|
15
|
|
Overall Study
102nd Week
|
15
|
14
|
|
Overall Study
114th Week
|
15
|
14
|
|
Overall Study
138th Week
|
15
|
14
|
|
Overall Study
186th Week
|
14
|
14
|
|
Overall Study
282nd Week
|
14
|
14
|
|
Overall Study
COMPLETED
|
14
|
14
|
|
Overall Study
NOT COMPLETED
|
3
|
2
|
Reasons for withdrawal
| Measure |
Group B (Lisinopril First, Then Placebo)
Started with Lisinopril 2.5 mg taken once a day. Then crossed over to Sugar Pill taken also once a day. The Lisinopril and the Sugar Pill were made indistinguishable in appearance.
|
Group A (Placebo First, Then Lisinopril)
Started with Sugar Pill taken once daily. Then crossed over to Lisinopril 2.5 mg taken once a day.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Physician Decision
|
0
|
1
|
Baseline Characteristics
The Effect and Safety of Lisinopril in Non-hypertensive Men With Infertility From Low Sperm Count
Baseline characteristics by cohort
| Measure |
Group B (Lisinopril First, Then Placebo)
n=17 Participants
Started with Lisinopril, crossed over to Placebo
|
Group A (Placebo First, Then Lisinopril)
n=16 Participants
Started with Sugar Pill, crossed over to Lisinopril
|
Total
n=33 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
Between 18 and 65 years
|
30.86 Years
STANDARD_DEVIATION 8.8 • n=5 Participants
|
26.93 Years
STANDARD_DEVIATION 7.3 • n=7 Participants
|
28.895 Years
STANDARD_DEVIATION 8.05 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
|
Region of Enrollment
Nigeria
|
17 participants
n=5 Participants
|
16 participants
n=7 Participants
|
33 participants
n=5 Participants
|
|
Height
|
1.51 metres
STANDARD_DEVIATION 0.4 • n=5 Participants
|
1.48 metres
STANDARD_DEVIATION 0.5 • n=7 Participants
|
1.495 metres
STANDARD_DEVIATION 0.45 • n=5 Participants
|
|
Weight
|
66.19 Kg
STANDARD_DEVIATION 11.2 • n=5 Participants
|
64.26 Kg
STANDARD_DEVIATION 10.3 • n=7 Participants
|
65.225 Kg
STANDARD_DEVIATION 10.75 • n=5 Participants
|
|
Duration of infertility
|
8.20 Years
STANDARD_DEVIATION 4.3 • n=5 Participants
|
7.77 Years
STANDARD_DEVIATION 3.1 • n=7 Participants
|
7.789 Years
STANDARD_DEVIATION 3.7 • n=5 Participants
|
|
Ejaculate volume
|
3.09 ml
STANDARD_DEVIATION 0.34 • n=5 Participants
|
3.01 ml
STANDARD_DEVIATION 0.23 • n=7 Participants
|
3.05 ml
STANDARD_DEVIATION 0.29 • n=5 Participants
|
|
Sperm cell count
|
5.29 Millions/ml
STANDARD_DEVIATION 2.6 • n=5 Participants
|
7.43 Millions/ml
STANDARD_DEVIATION 3.97 • n=7 Participants
|
6.36 Millions/ml
STANDARD_DEVIATION 3.29 • n=5 Participants
|
|
Sperm cell motility (%)
|
17.33 Per cent
STANDARD_DEVIATION 3.2 • n=5 Participants
|
22.12 Per cent
STANDARD_DEVIATION 4.4 • n=7 Participants
|
19.73 Per cent
STANDARD_DEVIATION 3.8 • n=5 Participants
|
|
Sperm cells with abnormal morphology (%)
|
42.91 Per cent
STANDARD_DEVIATION 5.1 • n=5 Participants
|
44.12 Per cent
STANDARD_DEVIATION 2.6 • n=7 Participants
|
43.52 Per cent
STANDARD_DEVIATION 3.85 • n=5 Participants
|
PRIMARY outcome
Timeframe: Week 96.Population: All the patients randomized into each group were included in the analysis on the basis of intention-to-treat (last value carried forward)
The seminal fluid characteristics were assessed twice before the entry of each patient and both at least two-weeks apart. The two values were averaged and recorded as baseline for week 0 while subsequent changes from the baseline were monitored during each of the scheduled visits at weeks 6, 12, 24, 48, 96, 102, 114, 138, 186 and 282. The two groups swopped treatments at the 96th week. The number of pregnancies achieved was also documented throughout the study period.
Outcome measures
| Measure |
Group B (Lisinopril First, Then Placebo)
n=17 Participants
Started with Lisinopril, crossed over to Placebo
|
Group A (Placebo First, Then Lisinopril)
n=16 Participants
Started with Sugar Pill, crossed over to Lisinopril
|
|---|---|---|
|
Changes From Baseline in the Seminal Fluid Characteristics Throughout the Study
|
3.47 ml
Standard Deviation 1.27
|
3.20 ml
Standard Deviation 1.19
|
PRIMARY outcome
Timeframe: Week 96Population: All the patients randomized into each group were analyzed on the basis of intention-to-treat
the number of sperm cells counted per milliliter volume of seminal fluid
Outcome measures
| Measure |
Group B (Lisinopril First, Then Placebo)
n=17 Participants
Started with Lisinopril, crossed over to Placebo
|
Group A (Placebo First, Then Lisinopril)
n=16 Participants
Started with Sugar Pill, crossed over to Lisinopril
|
|---|---|---|
|
Total Sperm Cell Count Per Milliliter of Seminal Fluid.
|
17.02 Millions/ml
Standard Deviation 5.02
|
7.17 Millions/ml
Standard Deviation 2.96
|
PRIMARY outcome
Timeframe: Week 96Population: All the patients randomized into each group was analyzed on the basis of intention-to-treat
This was determined as the proportion (percent) of the total sperm cells exhibiting both rhythmic and propulsive movements considered to be of normal intensity.
Outcome measures
| Measure |
Group B (Lisinopril First, Then Placebo)
n=17 Participants
Started with Lisinopril, crossed over to Placebo
|
Group A (Placebo First, Then Lisinopril)
n=16 Participants
Started with Sugar Pill, crossed over to Lisinopril
|
|---|---|---|
|
Proportion of Sperm Cells With Normal Motility (%)
|
31.08 Per cent
Standard Deviation 5.32
|
21.90 Per cent
Standard Deviation 3.66
|
PRIMARY outcome
Timeframe: Week 96Population: All the patients randomized into each group was analyzed on the basis of intention-to-treat.
Proportion (per cent) of sperm cells with abnormal appearance
Outcome measures
| Measure |
Group B (Lisinopril First, Then Placebo)
n=17 Participants
Started with Lisinopril, crossed over to Placebo
|
Group A (Placebo First, Then Lisinopril)
n=16 Participants
Started with Sugar Pill, crossed over to Lisinopril
|
|---|---|---|
|
Proportion of Sperm Cells With Abnormal Morphology (%)
|
15.95 per cent
Standard Deviation 4.290
|
44.73 per cent
Standard Deviation 5.61
|
PRIMARY outcome
Timeframe: Week 282Population: All the patients who were randomized into eacg group was analyzed on the basis of intention-to-treat
The volume in milliliters of seminal fluid produced per ejaculation.
Outcome measures
| Measure |
Group B (Lisinopril First, Then Placebo)
n=17 Participants
Started with Lisinopril, crossed over to Placebo
|
Group A (Placebo First, Then Lisinopril)
n=16 Participants
Started with Sugar Pill, crossed over to Lisinopril
|
|---|---|---|
|
Ejaculate Volume
|
3.73 ml
Standard Deviation 1.70
|
3.55 ml
Standard Deviation 1.86
|
PRIMARY outcome
Timeframe: Week 282Population: All the patients who were randomized into each group were analyzed on the basis of intention-to-treat.
The total number of sperm cells found in each milliliter of seminal fluid.
Outcome measures
| Measure |
Group B (Lisinopril First, Then Placebo)
n=17 Participants
Started with Lisinopril, crossed over to Placebo
|
Group A (Placebo First, Then Lisinopril)
n=16 Participants
Started with Sugar Pill, crossed over to Lisinopril
|
|---|---|---|
|
Total Sperm Cell Count
|
12.86 Millions/ml
Standard Deviation 4.61
|
13.81 Millions/ml
Standard Deviation 5.11
|
PRIMARY outcome
Timeframe: Week 282Population: All the patients who were randomized into each group were analyzed on the basis of intention-to-treat
The proportion (per cent) of the sperm cells exhibiting both rhythmic and propulsive movements considered to be of normal intensity.
Outcome measures
| Measure |
Group B (Lisinopril First, Then Placebo)
n=17 Participants
Started with Lisinopril, crossed over to Placebo
|
Group A (Placebo First, Then Lisinopril)
n=16 Participants
Started with Sugar Pill, crossed over to Lisinopril
|
|---|---|---|
|
Proportion of Sperm Cells With Normal Motility (%)
|
14.45 Per cent
Standard Deviation 2.88
|
29.99 Per cent
Standard Deviation 4.51
|
PRIMARY outcome
Timeframe: Week 282Population: All the patients who were randomized into each group were analyzed on the basis of intention-to-treat.
The proportion (per cent) of the total number of sperm cell with abnormal appearance.
Outcome measures
| Measure |
Group B (Lisinopril First, Then Placebo)
n=17 Participants
Started with Lisinopril, crossed over to Placebo
|
Group A (Placebo First, Then Lisinopril)
n=16 Participants
Started with Sugar Pill, crossed over to Lisinopril
|
|---|---|---|
|
Proportion of Sperm Cells With Abnormal Morphology (%)
|
28.55 Per cent
Standard Deviation 5.670
|
12.14 Per cent
Standard Deviation 5.78
|
SECONDARY outcome
Timeframe: At weeks 6, 12, 24, 48, 96, 102, 114,138, 186 and 282Population: All the patients who were randomized into each group were monitored for adverse events.
The patients were encouraged to report every event promptly by phone to one of the authors (NOG), no matter however minor.Blood pressure measurements were done with mercury sphygmomanometers fitted with adult-size cuffs (Accoson, England). Serum potassium levels were estimated using the flame photometric method as described by Davidson and Henry
Outcome measures
| Measure |
Group B (Lisinopril First, Then Placebo)
n=17 Participants
Started with Lisinopril, crossed over to Placebo
|
Group A (Placebo First, Then Lisinopril)
n=16 Participants
Started with Sugar Pill, crossed over to Lisinopril
|
|---|---|---|
|
Adverse Events Monitoring
|
0 participants
|
0 participants
|
Adverse Events
Events Reported During Treatment With Lisinopril
Events Reported During Treatment With Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Events Reported During Treatment With Lisinopril
n=33 participants at risk
All the events reported by patients in either group A or group B while receiving Lisinopril.
|
Events Reported During Treatment With Placebo
n=33 participants at risk
All the events reported by patients in either group A or group B while receiving the Sugar Pill.
|
|---|---|---|
|
Gastrointestinal disorders
Anorexia
|
12.1%
4/33 • Number of events 8 • Five years
The patients were interviewed during every scheduled appointment, contacted by phone calls and through sporadic home visits between appointments.
|
15.2%
5/33 • Number of events 6 • Five years
The patients were interviewed during every scheduled appointment, contacted by phone calls and through sporadic home visits between appointments.
|
|
Gastrointestinal disorders
Constipation
|
6.1%
2/33 • Number of events 2 • Five years
The patients were interviewed during every scheduled appointment, contacted by phone calls and through sporadic home visits between appointments.
|
3.0%
1/33 • Number of events 2 • Five years
The patients were interviewed during every scheduled appointment, contacted by phone calls and through sporadic home visits between appointments.
|
|
Musculoskeletal and connective tissue disorders
Chest pain
|
6.1%
2/33 • Number of events 3 • Five years
The patients were interviewed during every scheduled appointment, contacted by phone calls and through sporadic home visits between appointments.
|
6.1%
2/33 • Number of events 4 • Five years
The patients were interviewed during every scheduled appointment, contacted by phone calls and through sporadic home visits between appointments.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
12.1%
4/33 • Number of events 15 • Five years
The patients were interviewed during every scheduled appointment, contacted by phone calls and through sporadic home visits between appointments.
|
12.1%
4/33 • Number of events 11 • Five years
The patients were interviewed during every scheduled appointment, contacted by phone calls and through sporadic home visits between appointments.
|
|
Respiratory, thoracic and mediastinal disorders
Catarrh
|
9.1%
3/33 • Number of events 12 • Five years
The patients were interviewed during every scheduled appointment, contacted by phone calls and through sporadic home visits between appointments.
|
9.1%
3/33 • Number of events 8 • Five years
The patients were interviewed during every scheduled appointment, contacted by phone calls and through sporadic home visits between appointments.
|
|
Gastrointestinal disorders
Diarrhea
|
6.1%
2/33 • Number of events 7 • Five years
The patients were interviewed during every scheduled appointment, contacted by phone calls and through sporadic home visits between appointments.
|
9.1%
3/33 • Number of events 7 • Five years
The patients were interviewed during every scheduled appointment, contacted by phone calls and through sporadic home visits between appointments.
|
|
Vascular disorders
Dizziness
|
6.1%
2/33 • Number of events 4 • Five years
The patients were interviewed during every scheduled appointment, contacted by phone calls and through sporadic home visits between appointments.
|
6.1%
2/33 • Number of events 2 • Five years
The patients were interviewed during every scheduled appointment, contacted by phone calls and through sporadic home visits between appointments.
|
|
Gastrointestinal disorders
Epigastric pain
|
12.1%
4/33 • Number of events 5 • Five years
The patients were interviewed during every scheduled appointment, contacted by phone calls and through sporadic home visits between appointments.
|
6.1%
2/33 • Number of events 8 • Five years
The patients were interviewed during every scheduled appointment, contacted by phone calls and through sporadic home visits between appointments.
|
|
Infections and infestations
Fever
|
18.2%
6/33 • Number of events 22 • Five years
The patients were interviewed during every scheduled appointment, contacted by phone calls and through sporadic home visits between appointments.
|
24.2%
8/33 • Number of events 28 • Five years
The patients were interviewed during every scheduled appointment, contacted by phone calls and through sporadic home visits between appointments.
|
|
Nervous system disorders
Headache
|
18.2%
6/33 • Number of events 15 • Five years
The patients were interviewed during every scheduled appointment, contacted by phone calls and through sporadic home visits between appointments.
|
15.2%
5/33 • Number of events 9 • Five years
The patients were interviewed during every scheduled appointment, contacted by phone calls and through sporadic home visits between appointments.
|
|
Musculoskeletal and connective tissue disorders
Joint pains
|
12.1%
4/33 • Number of events 14 • Five years
The patients were interviewed during every scheduled appointment, contacted by phone calls and through sporadic home visits between appointments.
|
9.1%
3/33 • Number of events 9 • Five years
The patients were interviewed during every scheduled appointment, contacted by phone calls and through sporadic home visits between appointments.
|
|
General disorders
Malaise
|
12.1%
4/33 • Number of events 19 • Five years
The patients were interviewed during every scheduled appointment, contacted by phone calls and through sporadic home visits between appointments.
|
18.2%
6/33 • Number of events 15 • Five years
The patients were interviewed during every scheduled appointment, contacted by phone calls and through sporadic home visits between appointments.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
9.1%
3/33 • Number of events 7 • Five years
The patients were interviewed during every scheduled appointment, contacted by phone calls and through sporadic home visits between appointments.
|
6.1%
2/33 • Number of events 3 • Five years
The patients were interviewed during every scheduled appointment, contacted by phone calls and through sporadic home visits between appointments.
|
Additional Information
Dr. Anthony Mbah, Principal investigator
University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place