Effects of Glucagon-like-Peptide-1 Analogues on Sexuality

Study Overview
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Brief Summary
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This study is to investigate the effects of the GLP-1 analogue Liraglutide (combined with lifestyle interventions in comparison to lifestyle interventions only) on sexual desire, mood, quality of life, the reproductive axis, retinal vessel diameters, physical fitness and semen in overweight or obese men.

Detailed Description
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Glucagon-like peptide-1 (GLP-1) analogs are widely used for the treatment of type 2 diabetes mellitus due to its well-known insulinotropic effects as well as for the treatment of obesity due to its satiation-promoting and appetite- suppressant effects. The GLP-1 analog Liraglutide (Saxenda®) is approved in patients with obesity (BMI ≥ 30 kg/m2) or who are overweight (BMI ≥ 27 kg/m2) with additional comorbidities, such as prediabetes, diabetes mellitus type 2, arterial hypertension or dyslipidemia. Beside its influence on the reward for palatable food, several studies have shown that GLP-1 analogs modulate the rewarding effects of addictive drugs such as alcohol, nicotine and cocaine. As a further natural reward, sexual desire could be affected by GLP-1 analogs likewise. This study investigates the influence of GLP-1- analogs on sexuality in a population of overweight and obese participants. A treatment with Liraglutide combined with lifestyle modifications for weight reduction will be compared to weight reduction with conventional lifestyle modifications only. In the context of the increasing use of GLP-1-analogs, particularly in young people with reproductive desire, laboratory analyzes of the reproductive axis (hormones and sperm cells) will be part of this study to document a possible influence. Mood changes, physical activity and fitness and effects on microvascular endothelial functioning by measuring diameters of retinal vessels will be further investigated.

Official Title
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The Desire PLUS Study - Effects of Glucagon-like-Peptide-1 Analogues on Sexuality: a Prospective Open-label Study

Conditions
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Sexual Desire

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI ≥ 27 kg/m2 Willingness to lose weight by lifestyle changes only or by lifestyle changes plus liraglutide treatment as agreed in a routine clinical appointment Active sex life (sex with partner or masturbation ≥2x/month) Eugonadism (morning total testosterone ≥12mmol/l) Exclusion Criteria: Diabetes mellitus, HbA1c ≥ 6,5 % Previous use of GLP-1 analogous during last 2 months. Exogenous testosterone substitution Current illicit drug abuse

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Liraglutide Group<br>Liraglutide Group: receiving Liraglutide for weight management in addition to conventional weight management (= lifestyle intervention plus liraglutide). Conventional weight management is conducted according to clinical guidelines (in both groups) and includes nutritional and exercise counselling, counselling by motivational coaches and/ or psychological support. Participants in the Liraglutide group will inject the medication themselves. | |
| Lifestyle group<br>Lifestyle group: using conventional weight management (= lifestyle intervention only). Conventional weight management is conducted according to clinical guidelines (in both groups) and includes nutritional and exercise counselling, counselling by motivational coaches and/ or psychological support. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the German short version of the Sexual Desire Inventory (SDI-2) total score to assess sexual functioning | The SDI-2 consists of two items addressing frequency of sexual thoughts or activity, rated by a discrete score ranging from 0 to 7 (0 = not at all; 1 = once a month; 2 = once in two weeks; 3 = once a week; 4 = twice a week; 5 = three to four times a week; 6 = once a day; 7 = several times a day), and eight items rating the strengths of different types of sexual desires, rated by a continuous score ranging from 0 to 8 (0 = no desire to 8 = strong desire). The SDI-2 sum score ranges from 0 to 78. A positive score change indicates improvement of sexual desire. | At baseline (before start of treatment, at V1) and after 16 weeks of treatment (V2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the International Index of Erectile Function (IIEF-5) questionnaire to assess erectile function | The IIEF-5 is a 15-item self-evaluation scale; it provides pre-post treatment clinic evaluations of erectile function, orgasmic function, sexual desire, satisfaction in sexual intercourse and general satisfaction. | At baseline (before start of treatment, at V1) and after 16 weeks of treatment (V2) | 
| Change in the Patient Health Questionnaire (PHQ) -9 questionnaire to assess mood changes | The PHQ-9 tool may reflect patients' accounts of their experiences of depression and to assess severity of and treatment response. Each of the 9 items can be scored from 0 (not at all) to 3 (nearly every day). | At baseline (before start of treatment, at V1) and after 16 weeks of treatment (V2) | 
| Change in the Patient Health Questionnaire (EQ-5D-5L) questionnaire to assess quality of life | The EQ-5D descriptive system comprises five dimensions: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. The five levels in each dimension are worded as (1) 'not /no problems', (2) 'slight problems', (3) 'moderate problems', (4) 'severe problems', and (5) 'unable to' (mobility, self-care, usual activities), 'extreme' (pain/depression), or 'extremely' (anxiety/depression). The second part of the questionnaire comprises a standard vertical 20-cm VAS that is calibrated from 'the worst health you can imagine' (scored 0) at its base to 'the best health you can imagine' (scored 100) at its apex. | At baseline (before start of treatment, at V1) and after 16 weeks of treatment (V2) | 
| Change in retinal vessel diameters to assess microvascular endothelial functioning | Change in retinal vessel diameters with the Static Retinal Vessel Analyzer (SVA-T, Imedos Systems UG, Jena, Germany). The system consists of a fundus camera (Topcon TRC NW8) and analyzing software (Visualis 3.2, Imedos Systems UG), allowing non-invasive and non-mydriatic assessment of retinal vessel diameters. | At baseline (before start of treatment, at V1) and after 16 weeks of treatment (V2) | 
| Change in Oxytocin Level (IU) (hormone of the reproductive axis) | Oxytocin Level (hormone of the reproductive axis) will be measured in the blood. | At baseline (before start of treatment, at V1) and after 16 weeks of treatment (V2) | 
| Change in semen concentration | Change in semen concentration | At baseline (before start of treatment, at V1) and after 16 weeks of treatment (V2) | 
| Change in peak oxygen consumption during spiroergometry to assess physical fitness | Change in peak oxygen consumption during spiroergometry | At baseline (before start of treatment, at V1) and after 16 weeks of treatment (V2) | 
| Change in maximum heart rate during spiroergometry | Change in maximum heart rate during spiroergometry | At baseline (before start of treatment, at V1) and after 16 weeks of treatment (V2) | 
| Change in the Freiburg questionnaire for physical activity (FQPA) | The questionnaire consists of 12 items and allows a calculation of weighted metabolic equivalent tasks (MET) hours per week. The Physical Activity Questionnaire (FPAQ) is used to measure physical activity. Individuals are considered physically active when they achieved metabolic equivalent tasks (MET) minutes of 600 or more per week. | At baseline (before start of treatment, at V1) and after 16 weeks of treatment (V2) | 
| Change in Testosterone level (nmol/l) (hormone of the reproductive axis) | Testosterone level (hormone of the reproductive axis) will be measured in the blood. | At baseline (before start of treatment, at V1) and after 16 weeks of treatment (V2) | 
| Change in Estradiol level (pmol/l) (hormone of the reproductive axis) | Estradiol level (hormone of the reproductive axis) will be measured in the blood. | At baseline (before start of treatment, at V1) and after 16 weeks of treatment (V2) | 
| Change in Sex hormone-binding globulin (SHBG) level (nmol/l) (hormone of the reproductive axis) | Sex hormone-binding globulin (SHBG) level (hormone of the reproductive axis) will be measured in the blood. | At baseline (before start of treatment, at V1) and after 16 weeks of treatment (V2) | 
| Change in Luteinising hormone (LH) level (U/l) (hormone of the reproductive axis) | Luteinising hormone (LH) level (hormone of the reproductive axis) will be measured in the blood. | At baseline (before start of treatment, at V1) and after 16 weeks of treatment (V2) | 
| Change in Follicle stimulating hormone (LH) level (U/l) (hormone of the reproductive axis) | Follicle stimulating hormone level (hormone of the reproductive axis) will be measured in the blood. | At baseline (before start of treatment, at V1) and after 16 weeks of treatment (V2) | 
| Change in Prolactin level (yg/l) (hormone of the reproductive axis) | Prolactin level (hormone of the reproductive axis) will be measured in the blood. | At baseline (before start of treatment, at V1) and after 16 weeks of treatment (V2) | 
| Change in semen motility | Change in semen motility | At baseline (before start of treatment, at V1) and after 16 weeks of treatment (V2) | 
| Change in sperm fragmentation index (percentage of sperm with fragmented DNA) | Change in sperm fragmentation index (percentage of sperm with fragmented DNA) | At baseline (before start of treatment, at V1) and after 16 weeks of treatment (V2) | 
| Change in body weight (kg) | Body weight is measured during the bioelectrical impedance analysis. The InBody 720 device is used to perform the analysis. | At baseline (before start of treatment, at V1) and after 16 weeks of treatment (V2) | 
| Change in body fat mass (%) | Body fat mass is measured during the bioelectrical impedance analysis. The InBody 720 device is used to perform the analysis. | At baseline (before start of treatment, at V1) and after 16 weeks of treatment (V2) | 
| Change in total body water (l) | Total body water is measured during the bioelectrical impedance analysis. The InBody 720 device is used to perform the analysis. | At baseline (before start of treatment, at V1) and after 16 weeks of treatment (V2) | 
| Change in extracellular water (%) | Extracellular water is measured during the bioelectrical impedance analysis. The InBody 720 device is used to perform the analysis. | At baseline (before start of treatment, at V1) and after 16 weeks of treatment (V2) | 
| Change in intracellular water (%) | Intracellular water is measured during the bioelectrical impedance analysis. The InBody 720 device is used to perform the analysis. | At baseline (before start of treatment, at V1) and after 16 weeks of treatment (V2) | 
| Change in hip/waist ratio | Hip/waist ratio is measured during the bioelectrical impedance analysis. The InBody 720 device is used to perform the analysis. | At baseline (before start of treatment, at V1) and after 16 weeks of treatment (V2) | 
| Change in Basal metabolic rate ((kcal/24h) | Basal metabolic rate is measured during the bioelectrical impedance analysis. The InBody 720 device is used to perform the analysis. | At baseline (before start of treatment, at V1) and after 16 weeks of treatment (V2) | 
| Change in visceral fat (%) | Visceral fat is measured during the bioelectrical impedance analysis. The InBody 720 device is used to perform the analysis. | At baseline (before start of treatment, at V1) and after 16 weeks of treatment (V2) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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physical fitness, Glucagon-like-Peptide-1 (GLP-1), Glucagon-like peptide-1 (GLP-1) analogs, obesity, sexuality, Liraglutide (Saxenda®), obese men, reproductive axis, microvascular endothelial function, retinal vessels, physical activity, mood, sperm cells