Testosterone Treatment for Erectile Dysfunction and Multiple Sclerosis

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to determine the effects of testosterone treatment on erectile function, fatigue, depression, cognitive function, quality of life, urinary incontinence, pain, and damage to neurons in male Multiple Sclerosis patients with low testosterone, using questionnaires, blood samples and a rectal exam in volunteers 55 years and older.

Detailed Description
-----------------
Volunteers will be treated weekly with Xyosted 75 mg (given subcutaneously) for 3 months during which they will have 3 study visits, 6 weeks apart. The Baseline visit will include providing a blood sample, completing questionnaires, receiving training on the Xyosted auto-injector, and undergoing a rectal exam for participants 55 years and older. Visits 2 and 3 will also include collecting a blood sample and completing questionnaires. At Visit 3, the rectal exam for those age 55 years and older will be repeated.

Official Title
-----------------
Testosterone TReatment for Erectile Dysfunction in Male Multiple Sclerosis Patients With Low Testosterone (TTRED-MS Study)

Conditions
-----------------
Multiple Sclerosis, Erectile Dysfunction, Testosterone Deficiency

Intervention / Treatment
-----------------
* Drug: XYOSTED 75 milligram (mg) in 0.5 ML Auto-Injector


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males, age 18 years and older, with a definite diagnosis of multiple sclerosis. Low testosterone (<300 ng/dl) on two successive blood draws before 9:00 am Not in an intercurrent relapse. Sexually active. Have subjective complaints about erectile function and libido. Must be willing and able to get labs drawn, complete questionnaires (BDI, MFIS, MSNQ, SDMT, MSQOL, ADAM, AUASS, SHIM, MSHQ, ICIQ, UDI, IIQ, MPQ) and commit to site visits schedule. Exclusion Criteria: Males unable to fulfill the above criteria and all female patients. Males who have been on sex hormone treatment including androgens, estrogens, or anti-estrogens for hypogonadism or other medical condition during the 12 months prior to study. Males who have taken dehydroepiandrosterone (DHEA) during the 3 months prior to study. Patients who are taking anticoagulants or have thrombosis, serious cardiac, pulmonary, renal, gastrointestinal, hepatic, immunologic, infectious, neoplastic (with particular focus on patients with known or suspected estrogen or testosterone-dependent tumors), urologic disease especially prostatic hypertrophy/nodules and testicular mass, or insulin-dependent diabetes. Patients with an abnormal prostate as evidenced by known history of prostatic disease, symptoms suggestive of prostatic disease or elevated levels of prostatic specific antigen (PSA 4 ng/ml or higher) measured within the last 12 months. Patients with history or complaint of testicular mass. Patients with hematocrit greater than 50% Patients with major psychiatric illness Patients with active alcoholism. Patients with a history of drug abuse within the past five years. Patients with BMI ≥ 35 Patients with generalized skin disease that may affect absorption of testosterone (e.g. psoriasis) or a known skin intolerance to alcohol. Patients with history of pituitary disease. Patients with a cholesterol level greater than 300 mg/dl. Patients who are receiving or have received experimental therapies in the six months preceding enrollment. Patients who have history of positive titers to Human Immunodeficiency Virus (HIV)1 and 2; HTLV1; or Venereal Disease Research Laboratory (VDRL). Patients who have clinical evidence of Lyme disease. Males who are trying to get their partner pregnant. Patients on Finasteride Patients who are mentally or emotionally incompetent in the opinion of the examining neurologist or unable to give informed consent, or to understand and comply with the study protocol. Any other contraindications according to the manufacturer's exclusion criteria.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single open label
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment open label arm<br>Open-label feasibility study to determine the effects of testosterone (Xyosted 75mg subcutaneous once per week for 3 months) on erectile function in male Multiple Sclerosis patients with low testosterone. | Drug: XYOSTED 75 milligram (mg) in 0.5 ML Auto-Injector<br>* Self injection testosterone treatment<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the change in self-reported erectile function from baseline to 12-weeks after 12 weeks of treatment with XYOSTED in males with Multiple Sclerosis with low testosterone using Androgen Deficiency in the Aging Male (ADAM score). | Androgen Deficiency in the Aging Male (ADAM score) includes ten Yes or No questions, with an answer Yes to number 1 or 7 or if you answer Yes to more than 3 questions, you may have low Testosterone. | Change from baseline to 12 weeks | 
| Determine the change in self-reported erectile function from baseline to 12-weeks after 12 weeks of treatment with XYOSTED in males with Multiple Sclerosis with low testosterone using Sexual Health in Men (SHIM score). | Sexual Health in Men (SHIM score) with a range of 1 to 25 with a higher number representing less erectile dysfunction. | Change from baseline to 12 weeks | 
| Determine the change in self-reported erectile function from baseline to 12-weeks after 12 weeks of treatment with XYOSTED in males with Multiple Sclerosis with low testosterone using Male Sexual Health Questionnaire short form (MSHQ-SF). | Male Sexual Health Questionnaire short form (MSHQ-SF) with a range of 1 to 15 with a higher number representing better ejaculatory function, in addition to one bother/satisfaction question, scored 1 to 5 where the higher represents more bothersome. | Change from baseline to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure the change in self-reported fatigue from baseline to 12-weeks after 12 weeks of treatment with XYOSTED in males with Multiple Sclerosis with low testosterone using the Modified Fatigue Impact Scale (MFIS). | Modified Fatigue Impact Scale (MFIS) with a range of 0 to 84 with a higher number representing greater impact of fatigue on a person's activities. | Change from baseline to 12 weeks | 
| Measure the change in self-reported depression from baseline to 12-weeks after 12 weeks of treatment with XYOSTED in males with Multiple Sclerosis with low testosterone using the Beck Depression Inventory (BDI). | Beck Depression Inventory (BDI) with a range of 0 to 63 with a higher number representing higher level of depression. | Change from baseline to 12 weeks | 
| Measure the change in cognitive function from baseline to 12-weeks after 12 weeks of treatment with XYOSTED in males with Multiple Sclerosis with low testosterone using the Symbol Digit Modalities Test (SDMT). | Symbol Digit Modalities Test (SDMT) which provides a score for as many items as can be completed in 90 seconds (t-score calculated using age, sex and education normative data), with a higher score representing a better performance. | Change from baseline to 12 weeks | 
| Measure the change in cognitive function from baseline to 12-weeks after 12 weeks of treatment with XYOSTED in males with Multiple Sclerosis with low testosterone using the Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNQ). | Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNQ) with a range of 0 to 30 with a higher number representing worse cognitive function. | Change from baseline to 12 weeks | 
| Measure the change in self-reported overall quality of life from baseline to 12-weeks after 12 weeks of treatment with XYOSTED in males with Multiple Sclerosis with low testosterone using the Multiple Sclerosis Quality of Life Scale (MSQOL-54). | Multiple Sclerosis Quality of Life Scale (MSQOL-54) which goes from 0 to 100 with a higher score indicating a better quality of life. | Change from baseline to 12 weeks | 
| Measure the change in self-reported urinary incontinence from baseline to 12-weeks after 12 weeks of treatment with XYOSTED in males with Multiple Sclerosis with low testosterone using the American Urological Association Symptom Score (AUASS). | The American Urological Association Symptom Score (AUASS) with a range of 0 to 35 with a higher number representing more severe enlarged prostate symptoms. | Change from baseline to 12 weeks | 
| Measure the change in self-reported urinary incontinence after 12 weeks of treatment with XYOSTED in males with Multiple Sclerosis with low testosterone using International Consultation on Incontinence Questionnaire short form (ICIQ-SF). | International Consultation on Incontinence Questionnaire short form (ICIQ-SF) with a range of 0 to 21 with a higher number representing greater impairment from incontinence. | Change from baseline to 12 weeks | 
| Measure the change in self-reported urinary incontinence from baseline to 12-weeks after 12 weeks of treatment with XYOSTED in males with Multiple Sclerosis with low testosterone using Urogenital Distress Inventory short form (UDI-6). | Urogenital Distress Inventory short form (UDI-6) with a range of 0 to 100 with a higher number representing higher the disability. | Change from baseline to 12 weeks | 
| Measure the change in self-reported urinary incontinence from baseline to 12-weeks after 12 weeks of treatment with XYOSTED in males with Multiple Sclerosis with low testosterone using Incontinence Impact Questionnaire short form (IIQ-7). | Incontinence Impact Questionnaire short form (IIQ-7) with a range of 0 to 100 with a higher number representing greater impact by urinary incontinence on the person's life. | Change from baseline to 12 weeks | 
| Measure the change in self-reported pain from baseline to 12-weeks after 12 weeks of treatment with XYOSTED in males with Multiple Sclerosis with low testosterone using the McGill Pain Questionnaire (MPQ). | McGill Pain Questionnaire (MPQ) with a range of 0 to 78 with a higher number representing greater pain. | Change from baseline to 12 weeks | 
| Measure the change in Multiple Sclerosis lesions, indirectly from baseline to 12-weeks after 12 weeks of treatment with XYOSTED in males with Multiple Sclerosis with low testosterone using the serum levels of neurofilament-light chains (NF-L). | The serum levels of neurofilament-light chains (NF-L) with a higher level representing more neuro-axonal injury in the central nervous system. | Change from baseline to 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Multiple Sclerosis, Erectile Dysfunction, Testosterone Deficiency