Male Infertility, Obesity, Weight Loss
Conditions
Keywords
Male Infertility, Obesity
Brief summary
The purpose of this study is to determine the physiological effects of weight loss on seminal parameters in male participants with reduced reproductive capacity. Learning more about the physiological role of weight loss on reproductive function and metabolic profile of overweight and obese men may give us a better understanding of male fertility and improve the management of patients with reduced fertility. The effects of weight loss on seminal quality are not well understood.
Detailed description
Participants will receive dietary supplements or National Health Service (NHS) advice on healthy eating to achieve weight loss.
Interventions
DIETARY_SUPPLEMENTLow Energy Diet
Caloric restriction to achieve weight loss
OTHERNHS advice on healthy eating
Advice on energy requirements as per the British Dietetic Association
Sponsors
Imperial College London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Intervention model description
2 sub-studies Study A (men with a normal sperm concentration) Study B (men with a low sperm concentration)
Eligibility
Sex/Gender
MALE
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Body mass index (BMI) ≥ 30 kg/m\^2 \[Part: 1, 2& 3\] * Evidence of reduced reproductive capacity (e.g. reduced sperm concentration \[applicable for study B\]
Exclusion criteria
* History of undescended testes, testicular surgery or mumps infection * Hormonal therapy such as testosterone or selective oestrogen receptor modulators * History of systemic cytotoxic therapy or pelvic radiotherapy * Chronic systemic disease, such as cardiac, renal or liver failure * At least one of the following: Alcohol intake \>30 units per week Smoking daily Recreational drug use at a frequency not less than weekly * Acute illness likely to affect the result of study * Impaired ability to provide full consent to take part in the study * An occupation requiring strenuous physical exercise that may require a high energy diet
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sperm Concentration | 16 weeks | The number of sperm per millimeter of semen. Sperm concentration is an important factor affecting male fertility. It is calculated on a standard semen analysis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progressive Motility | 16 weeks | This type of motility refers to sperm that swim progressively, mostly in a straight line or large circles. |
| DNA Fragmentation Index (DFI) | 16 weeks | Percentage of sperm with fragmented DNA |
| Testosterone | 16 weeks | Testosterone is the primary androgen in men and is synthesized in the testes. It can be measured in the serum. |
| Sex Hormone-Binding Globulin (SHBG) | 16 weeks | SHBG is a protein that is produced by the liver and binds tightly to the hormones testosterone, dihydrotestosterone (DHT) and oestradiol, and transports them in the blood in an inactive form. |
| Total Motility | 16 weeks | Total motility refers to the percentage of sperm making any sort of movement. |
| Morphology | 16 weeks | the percentage of sperm that appear normal when semen is viewed under a microscope |
| Luteinizing Hormone (LH) | 16 weeks | LH produced in the pituitary gland, stimulates the leydig cells in the testes to produce testosterone. |
| Follicle Stimulating Hormone (FSH) | 16 weeks | FSH produced in the pituitary gland, stimulates the testes to produce mature sperm. |
| Reactive Oxygen Species (ROS) | 16 weeks | ROS is measured by oxidative colour change of luminol per second per million sperm. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Low Energy Diet Commercially available diet products
Low Energy Diet: Caloric restriction to achieve weight loss | 32 |
| NHS Advice on Healthy Eating Dietary / lifestyle advice programme
NHS advice on healthy eating: Advice on energy requirements as per the British Dietetic Association | 35 |
| Total | 67 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Study A (Men With a Normal Sperm Conc.) | Withdrawal by Subject | 2 | 2 |
| Study B (Men With a Low Sperm Conc.) | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Total | NHS Advice on Healthy Eating | Low Energy Diet | — |
|---|---|---|---|---|
| Age, Categorical Study A (men with a normal sperm concentration) <=18 years | 0 Participants | 0 Participants | 0 Participants | — |
| Age, Categorical Study A (men with a normal sperm concentration) >=65 years | 0 Participants | 0 Participants | 0 Participants | — |
| Age, Categorical Study A (men with a normal sperm concentration) Between 18 and 65 years | 24 Participants | 12 Participants | 12 Participants | — |
| Age, Categorical Study B (men with a low sperm concentration) <=18 years | 0 Participants | 0 Participants | 0 Participants | — |
| Age, Categorical Study B (men with a low sperm concentration) >=65 years | 0 Participants | 0 Participants | 0 Participants | — |
| Age, Categorical Study B (men with a low sperm concentration) Between 18 and 65 years | 43 Participants | 23 Participants | 20 Participants | — |
| Age, Continuous Study A (men with a normal sperm concentration) | 39.8 Years STANDARD_DEVIATION 8 | 39.4 Years STANDARD_DEVIATION 6.4 | 40.2 Years STANDARD_DEVIATION 9.6 | — |
| Age, Continuous Study B (men with a low sperm concentration) | 38.6 Years STANDARD_DEVIATION 7.1 | 39.5 Years STANDARD_DEVIATION 7.5 | 37.7 Years STANDARD_DEVIATION 6.6 | — |
| Body Mass Index (BMI) Study A (men with a normal sperm concentration) | 35.8 kg/m^2 STANDARD_DEVIATION 3.3 | 36.2 kg/m^2 STANDARD_DEVIATION 2.4 | 35.3 kg/m^2 STANDARD_DEVIATION 4.1 | — |
| Body Mass Index (BMI) Study B (men with a low sperm concentration) | 38 kg/m^2 STANDARD_DEVIATION 5.3 | 38 kg/m^2 STANDARD_DEVIATION 6.3 | 38 kg/m^2 STANDARD_DEVIATION 4 | — |
| DNA Fragmentation Index Study A (men with a normal sperm concentration) | 13.8 percentage of sperm with fragmented DNA STANDARD_DEVIATION 9.5 | 15.9 percentage of sperm with fragmented DNA STANDARD_DEVIATION 6.7 | 11.9 percentage of sperm with fragmented DNA STANDARD_DEVIATION 13.1 | — |
| DNA Fragmentation Index Study B (men with a low sperm concentration) | 13.6 percentage of sperm with fragmented DNA STANDARD_DEVIATION 8.9 | 12.1 percentage of sperm with fragmented DNA STANDARD_DEVIATION 9.5 | 15.8 percentage of sperm with fragmented DNA STANDARD_DEVIATION 7.7 | — |
| Follicle Stimulating Hormone (FSH) Study A (men with a normal sperm concentration) | 4.3 IU/l STANDARD_DEVIATION 2.8 | 4.4 IU/l STANDARD_DEVIATION 1.9 | 4.2 IU/l STANDARD_DEVIATION 2.6 | — |
| Follicle Stimulating Hormone (FSH) Study B (men with a low sperm concentration) | 5.3 IU/l STANDARD_DEVIATION 2.7 | 5 IU/l STANDARD_DEVIATION 2.5 | 5.6 IU/l STANDARD_DEVIATION 2.9 | — |
| Luteinizing Hormone (LH) Study A (men with a normal sperm concentration) | 3.3 IU/l STANDARD_DEVIATION 1.4 | 3.5 IU/l STANDARD_DEVIATION 1.7 | 3.2 IU/l STANDARD_DEVIATION 1 | — |
| Luteinizing Hormone (LH) Study B (men with a low sperm concentration) | 4 IU/l STANDARD_DEVIATION 1.2 | 4.3 IU/l STANDARD_DEVIATION 1.5 | 3.7 IU/l STANDARD_DEVIATION 0.9 | — |
| Morphology Study A (men with a normal sperm concentration) | 1.7 percentage of sperm of normal morphology STANDARD_DEVIATION 1.3 | 1.8 percentage of sperm of normal morphology STANDARD_DEVIATION 1.4 | 1.6 percentage of sperm of normal morphology STANDARD_DEVIATION 1.3 | — |
| Morphology Study B (men with a low sperm concentration) | 0.7 percentage of sperm of normal morphology STANDARD_DEVIATION 0.8 | 1 percentage of sperm of normal morphology STANDARD_DEVIATION 0.8 | 0.4 percentage of sperm of normal morphology STANDARD_DEVIATION 0.7 | — |
| Progressive motility Study A (men with a normal sperm concentration) | 43 percentage of progressively motile sperm STANDARD_DEVIATION 12 | 45 percentage of progressively motile sperm STANDARD_DEVIATION 8 | 41 percentage of progressively motile sperm STANDARD_DEVIATION 16 | — |
| Progressive motility Study B (men with a low sperm concentration) | 31.1 percentage of progressively motile sperm STANDARD_DEVIATION 13.9 | 33.4 percentage of progressively motile sperm STANDARD_DEVIATION 14.5 | 28.7 percentage of progressively motile sperm STANDARD_DEVIATION 13.2 | — |
| Race/Ethnicity, Customized Arab | 7 Participants | 1 Participants | 6 Participants | — |
| Race/Ethnicity, Customized Asian | 16 Participants | 9 Participants | 7 Participants | — |
| Race/Ethnicity, Customized Black | 1 Participants | 1 Participants | 0 Participants | — |
| Race/Ethnicity, Customized Mixed | 2 Participants | 2 Participants | 0 Participants | — |
| Race/Ethnicity, Customized Other | 2 Participants | 0 Participants | 2 Participants | — |
| Race/Ethnicity, Customized White | 39 Participants | 22 Participants | 17 Participants | — |
| Reactive oxygen species (ROS) Study A (men with a normal sperm concentration) | — | — | — | — RLU/sec/million sperm |
| Reactive oxygen species (ROS) Study B (men with a low sperm concentration) | 7.1 RLU/sec/million sperm | 3.6 RLU/sec/million sperm | 8.6 RLU/sec/million sperm | — |
| Region of Enrollment United Kingdom | 67 participants | 35 participants | 32 participants | — |
| Semen volume Study A (men with a normal sperm concentration) | 3.6 ml STANDARD_DEVIATION 1.3 | 3.9 ml STANDARD_DEVIATION 1.1 | 3.3 ml STANDARD_DEVIATION 1.4 | — |
| Semen volume Study B (men with a low sperm concentration) | 3.4 ml STANDARD_DEVIATION 1.6 | 3.3 ml STANDARD_DEVIATION 1.4 | 3.7 ml STANDARD_DEVIATION 1.8 | — |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | — |
| Sex: Female, Male Male | 67 Participants | 35 Participants | 32 Participants | — |
| Sex hormone-binding globulin (SHBG) Study A (men with a normal sperm concentration) | 23.5 nmol/l STANDARD_DEVIATION 8.4 | 25.2 nmol/l STANDARD_DEVIATION 8.7 | 21.8 nmol/l STANDARD_DEVIATION 8.1 | — |
| Sex hormone-binding globulin (SHBG) Study B (men with a low sperm concentration) | 23.2 nmol/l STANDARD_DEVIATION 10.1 | 24.8 nmol/l STANDARD_DEVIATION 9.6 | 21.4 nmol/l STANDARD_DEVIATION 10.6 | — |
| Sperm concentration Study A (men with a normal sperm concentration) | 46.2 million sperms/mL STANDARD_DEVIATION 19.8 | 54.2 million sperms/mL STANDARD_DEVIATION 21.3 | 38.3 million sperms/mL STANDARD_DEVIATION 15 | — |
| Sperm concentration Study B (men with a low sperm concentration) | 7.6 million sperms/mL STANDARD_DEVIATION 7.9 | 9.8 million sperms/mL STANDARD_DEVIATION 10 | 5.3 million sperms/mL STANDARD_DEVIATION 3.4 | — |
| Testosterone Study A (men with a normal sperm concentration) | 12.5 nmol/l STANDARD_DEVIATION 3.4 | 12.3 nmol/l STANDARD_DEVIATION 2.5 | 12.7 nmol/l STANDARD_DEVIATION 4.2 | — |
| Testosterone Study B (men with a low sperm concentration) | 13.4 nmol/l STANDARD_DEVIATION 5.1 | 14.6 nmol/l STANDARD_DEVIATION 5 | 12.6 nmol/l STANDARD_DEVIATION 5.1 | — |
| Total motility Study A (men with a normal sperm concentration) | 50 percentage of sperm that is motile STANDARD_DEVIATION 13 | 52 percentage of sperm that is motile STANDARD_DEVIATION 8 | 48 percentage of sperm that is motile STANDARD_DEVIATION 17 | — |
| Total motility Study B (men with a low sperm concentration) | 36 percentage of sperm that is motile STANDARD_DEVIATION 15 | 40 percentage of sperm that is motile STANDARD_DEVIATION 15.5 | 35 percentage of sperm that is motile STANDARD_DEVIATION 13.8 | — |
| Waist circumference Study A (men with a normal sperm concentration) | 118.8 Centimetres STANDARD_DEVIATION 8.4 | 119.5 Centimetres STANDARD_DEVIATION 9.1 | 117.3 Centimetres STANDARD_DEVIATION 7.6 | — |
| Waist circumference Study B (men with a low sperm concentration) | 122.1 Centimetres STANDARD_DEVIATION 11.5 | 120.9 Centimetres STANDARD_DEVIATION 12.9 | 123.4 Centimetres STANDARD_DEVIATION 9.7 | — |
| Weight Study A (men with a normal sperm concentration) | 112.6 Kilograms STANDARD_DEVIATION 11.4 | 114.1 Kilograms STANDARD_DEVIATION 11 | 109.5 Kilograms STANDARD_DEVIATION 10.8 | — |
| Weight Study B (men with a low sperm concentration) | 116.9 Kilograms STANDARD_DEVIATION 19.7 | 117 Kilograms STANDARD_DEVIATION 21.9 | 116.8 Kilograms STANDARD_DEVIATION 17.3 | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 36 | 0 / 37 |
| other Total, other adverse events | 0 / 36 | 0 / 37 |
| serious Total, serious adverse events | 0 / 36 | 0 / 37 |
Outcome results
Primary
Sperm Concentration
The number of sperm per millimeter of semen. Sperm concentration is an important factor affecting male fertility. It is calculated on a standard semen analysis
Time frame: 16 weeks
Population: The overall number of participants analyzed refers to the total number after combining the two sub-studies
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Energy Diet | Sperm Concentration | Study A (men with normal sperm concentration) | 53.6 million sperms/mL | Standard Deviation 36.4 |
| Low Energy Diet | Sperm Concentration | Study B (men with low sperm concentration) | 20.1 million sperms/mL | Standard Deviation 59.16 |
| NHS Advice on Healthy Eating | Sperm Concentration | Study A (men with normal sperm concentration) | 58.5 million sperms/mL | Standard Deviation 32.8 |
| NHS Advice on Healthy Eating | Sperm Concentration | Study B (men with low sperm concentration) | 15 million sperms/mL | Standard Deviation 16.8 |
Secondary
DNA Fragmentation Index (DFI)
Percentage of sperm with fragmented DNA
Time frame: 16 weeks
Population: The overall number of participants analyzed refers to the total number after combining the two sub-studies.~Some participants in Study B were not assessed for this measure due to sperm concentrations that were too low to measure DNA fragmentation index.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Energy Diet | DNA Fragmentation Index (DFI) | Study A (men with a normal sperm concentration) | 7.7 Percentage of sperm with fragmented DNA | Standard Deviation 8.7 |
| Low Energy Diet | DNA Fragmentation Index (DFI) | study B (men with a low sperm concentration) | 18.4 Percentage of sperm with fragmented DNA | Standard Deviation 11.7 |
| NHS Advice on Healthy Eating | DNA Fragmentation Index (DFI) | Study A (men with a normal sperm concentration) | 19.8 Percentage of sperm with fragmented DNA | Standard Deviation 9.6 |
| NHS Advice on Healthy Eating | DNA Fragmentation Index (DFI) | study B (men with a low sperm concentration) | 11.2 Percentage of sperm with fragmented DNA | Standard Deviation 11 |
Secondary
Follicle Stimulating Hormone (FSH)
FSH produced in the pituitary gland, stimulates the testes to produce mature sperm.
Time frame: 16 weeks
Population: The overall number of participants analyzed refers to the total number after combining the two sub-studies.~One participant in Low Energy Diet arm in study B did not have this measurement due to insufficient sample.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Energy Diet | Follicle Stimulating Hormone (FSH) | Study A (men with a normal sperm concentration) | 3.8 IU/l | Standard Deviation 2.1 |
| Low Energy Diet | Follicle Stimulating Hormone (FSH) | Study B (men with a low sperm concentration) | 5.4 IU/l | Standard Deviation 2.6 |
| NHS Advice on Healthy Eating | Follicle Stimulating Hormone (FSH) | Study A (men with a normal sperm concentration) | 4.5 IU/l | Standard Deviation 2.2 |
| NHS Advice on Healthy Eating | Follicle Stimulating Hormone (FSH) | Study B (men with a low sperm concentration) | 5 IU/l | Standard Deviation 2.4 |
Secondary
Luteinizing Hormone (LH)
LH produced in the pituitary gland, stimulates the leydig cells in the testes to produce testosterone.
Time frame: 16 weeks
Population: The overall number of participants analyzed refers to the total number after combining the two sub-studies.~One participant in Low Energy Diet arm in study B did not have this measurement due to insufficient sample.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Energy Diet | Luteinizing Hormone (LH) | Study A (men with a normal sperm concentration) | 3.3 IU/l | Standard Deviation 1.4 |
| Low Energy Diet | Luteinizing Hormone (LH) | Study B (men with a low sperm concentration) | 3.5 IU/l | Standard Deviation 1.4 |
| NHS Advice on Healthy Eating | Luteinizing Hormone (LH) | Study A (men with a normal sperm concentration) | 2.8 IU/l | Standard Deviation 1.2 |
| NHS Advice on Healthy Eating | Luteinizing Hormone (LH) | Study B (men with a low sperm concentration) | 3.7 IU/l | Standard Deviation 1.5 |
Secondary
Morphology
the percentage of sperm that appear normal when semen is viewed under a microscope
Time frame: 16 weeks
Population: The overall number of participants analyzed refers to the total number after combining the two sub-studies.~Some participants in Study B were not assessed for this measure due to sperm concentrations that were too low to measure morphology.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Energy Diet | Morphology | Study A (men with a normal sperm concentration) | 1.2 percentage of sperm of normal morphology | Standard Deviation 1.1 |
| Low Energy Diet | Morphology | Study B (men with a low sperm concentration) | 0.6 percentage of sperm of normal morphology | Standard Deviation 0.6 |
| NHS Advice on Healthy Eating | Morphology | Study A (men with a normal sperm concentration) | 1.9 percentage of sperm of normal morphology | Standard Deviation 1.7 |
| NHS Advice on Healthy Eating | Morphology | Study B (men with a low sperm concentration) | 1.3 percentage of sperm of normal morphology | Standard Deviation 1.7 |
Secondary
Progressive Motility
This type of motility refers to sperm that swim progressively, mostly in a straight line or large circles.
Time frame: 16 weeks
Population: The overall number of participants analyzed refers to the total number after combining the two sub-studies.~Some participants in Study B were not assessed for this measure due to sperm concentrations that were too low to measure progressive motility.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Energy Diet | Progressive Motility | study B (men with a low sperm concentration) | 42.8 percentage of progressively motile sperm | Standard Deviation 14.1 |
| Low Energy Diet | Progressive Motility | Study A (men with a normal sperm concentration) | 53.3 percentage of progressively motile sperm | Standard Deviation 10.4 |
| NHS Advice on Healthy Eating | Progressive Motility | Study A (men with a normal sperm concentration) | 53.9 percentage of progressively motile sperm | Standard Deviation 6.1 |
| NHS Advice on Healthy Eating | Progressive Motility | study B (men with a low sperm concentration) | 39.6 percentage of progressively motile sperm | Standard Deviation 17 |
Secondary
Reactive Oxygen Species (ROS)
ROS is measured by oxidative colour change of luminol per second per million sperm.
Time frame: 16 weeks
Population: ROS was only measured in Study B. Some participants in Study B were not assessed for this measure due to sperm concentrations that were too low to measure ROS.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low Energy Diet | Reactive Oxygen Species (ROS) | 13 RLU/sec/million sperm |
| NHS Advice on Healthy Eating | Reactive Oxygen Species (ROS) | 5 RLU/sec/million sperm |
Secondary
Sex Hormone-Binding Globulin (SHBG)
SHBG is a protein that is produced by the liver and binds tightly to the hormones testosterone, dihydrotestosterone (DHT) and oestradiol, and transports them in the blood in an inactive form.
Time frame: 16 weeks
Population: The overall number of participants analyzed refers to the total number after combining the two sub-studies.~One participant in Low Energy Diet arm in study B did not have this measurement due to insufficient sample.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Energy Diet | Sex Hormone-Binding Globulin (SHBG) | (men with a normal sperm concentration) | 30.2 nmol/l | Standard Deviation 12.6 |
| Low Energy Diet | Sex Hormone-Binding Globulin (SHBG) | study B (men with a low sperm concentration) | 24.2 nmol/l | Standard Deviation 12.4 |
| NHS Advice on Healthy Eating | Sex Hormone-Binding Globulin (SHBG) | (men with a normal sperm concentration) | 26.4 nmol/l | Standard Deviation 7 |
| NHS Advice on Healthy Eating | Sex Hormone-Binding Globulin (SHBG) | study B (men with a low sperm concentration) | 22.6 nmol/l | Standard Deviation 8.1 |
Secondary
Testosterone
Testosterone is the primary androgen in men and is synthesized in the testes. It can be measured in the serum.
Time frame: 16 weeks
Population: The overall number of participants analyzed refers to the total number after combining the two sub-studies.~One participant in Low Energy Diet arm in study B did not have this measurement due to insufficient sample.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Energy Diet | Testosterone | Study A (men with a normal sperm concentration) | 13.6 nmol/l | Standard Deviation 5 |
| Low Energy Diet | Testosterone | study B (men with a low sperm concentration) | 15.6 nmol/l | Standard Deviation 6.2 |
| NHS Advice on Healthy Eating | Testosterone | Study A (men with a normal sperm concentration) | 12.4 nmol/l | Standard Deviation 2.8 |
| NHS Advice on Healthy Eating | Testosterone | study B (men with a low sperm concentration) | 13.7 nmol/l | Standard Deviation 4.1 |
Secondary
Total Motility
Total motility refers to the percentage of sperm making any sort of movement.
Time frame: 16 weeks
Population: The overall number of participants analyzed refers to the total number after combining the two sub-studies.~Some participants in Study B were not assessed for this measure due to sperm concentrations that were too low to measure total motility.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Energy Diet | Total Motility | men with a normal sperm concentration | 59.5 percentage of sperm that is motile | Standard Deviation 9.6 |
| Low Energy Diet | Total Motility | men with a low sperm concentration | 48.9 percentage of sperm that is motile | Standard Deviation 12 |
| NHS Advice on Healthy Eating | Total Motility | men with a normal sperm concentration | 60.8 percentage of sperm that is motile | Standard Deviation 6.3 |
| NHS Advice on Healthy Eating | Total Motility | men with a low sperm concentration | 45.4 percentage of sperm that is motile | Standard Deviation 16.1 |