Oral Testosterone for Fatigue in Male Multiple Sclerosis Patients

A Randomized, Controlled Crossover Trial Evaluating Oral Testosterone in the Treatment of Fatigue in Male Multiple Sclerosis Patients

Fatigue is one of the most frequent symptoms reported by multiple sclerosis (MS) patients and is often a significant source of disability. Unlike normal fatigue, multiple sclerosis related fatigue (MSRF) occurs independently of activity level, suggesting that it is due to dysfunction in the neural pathways that regulate the perception of energy although the precise cause is still not understood. While MSRF can be managed through lifestyle modifications and with drug treatment, these measures are commonly either ineffective or only partially effective.

Administration of the male sex hormone testosterone has been shown to improve energy levels in males with testosterone-deficiency states. Testosterone also reduces fatigue in patients with other medical conditions not associated with low testosterone levels, suggesting that this treatment may also be useful in symptomatic control of MSRF.

This proposed seven-month long clinical trial is designed to test the hypothesis that administration of oral testosterone tablets to male MS patients will result in an improvement of fatigue relative to the administration of placebo tablets. As fatigue is frequently reported by MS patients to be one of their most frustrating and disabling symptoms, any proven additional treatment option for MSRF would be beneficial in improving quality of life.

Study Overview

• Status: Terminated
• Conditions: Multiple Sclerosis; Fatigue
• Intervention / Treatment: Drug: Testosterone undecanoate; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A1R9
      • Health Sciences Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• All adult male (18-65 years old) patients are eligible. Patients over > 65 years will be excluded due to increased risk of prostatic hypertrophy or carcinoma in that age group.
• Patients must have diagnosis of MS using the 2005 revised McDonald Criteria.
• Patients must have an EDSS score ≤ 6.5.
• Patients must have a baseline MFIS score ≥ 45 (i.e.: those patients with fatigue).
• Patients must consent to participate in the study after a discussion of the potential risks and benefits of study participation with their physician. This consent must acknowledge that testosterone administration in MS is experimental and of no proven benefit.
• Patients must not be on any other agents to specifically treat MSRF (modafinil [Alertec®], amantadine, methylphenidate [Ritalin®, Ritalin SR®, Concerta®].

Exclusion Criteria:

• Previous or current testosterone administration.
• Any Health Canada approved indication for testosterone administration.
• Known hypersensitivity any component of the testosterone undecanoate (Andriol®) formulation including soy.
• History of relapse in the past 3 months.
• History of prostate hypertrophy or prostate carcinoma.
• History of breast cancer.
• Moderate or severe prostate symptoms (International Prostate Symptom Score [IPSS] ≥ 8).
• All patients ≥ 50 years old (or ≥ 40 years old if history of prostate cancer/prostate hypertrophy in a first-degree relative or if African-Canadian) will be require a urological assessment including prostate specific antigen (PSA) and digital rectal exam (DRE). Such patients will be excluded if they have a high PSA level or if they have a palpable prostate nodule. Abnormal PSA levels will be determined using standard age-specific cut-off levels.
• Other serious medical comorbidities including: any other cancer or myelodysplastic syndrome, anemia or polycythemia of any cause, vascular risk factors (including hypertension, dyslipidemia, myocardial infarction, stroke, peripheral vascular disease, atrial fibrillation, other hypercoaguable state or thrombotic risk factor), serious kidney or liver disease, diabetes, obstructive sleep apnea or serious psychiatric disease.
• History of current alcohol misuse.
• Recent major surgery.
• Use of the following medications whose metabolism may be altered by TT: warfarin, corticosteroids, propranolol, cyclosporine or St. John's Wort.81
• Patients on cyclophosphamide or mitoxantrone (Novantrone®) chemotherapy for MS will be excluded. Patients on other approved disease-modifying therapies for MS (interferon-β1a [Avonex®, Rebif®], interferon-β1b [Betaseron®], glatiramer acetate [Copaxone®] and natalizumab [Tysabri®]) can participate in this trial provided they have been on these therapies for at least six months at a stable dose.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Sugar pill	Drug: placebo; twice daily
Experimental: Testosterone undecanoate	Drug: Testosterone undecanoate; 40 mg twice daily; Other Names: Andriol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in fatigue (measured with Modified Fatigue Impact Scale [M-FIS])	baseline and 12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in fatigue as measured on a visual analog scale (VAS)	baseline and 12 weeks
Quality of life as measured with the Aging Males' Symptoms (AMS) scale	baseline and 12 weeks
Neurological status as measured with the Expanded Disability Status Scale (EDSS)	baseline and 12 weeks
Number of participants with , type and severity of adverse events	12 weeks

Collaborators and Investigators

• Sponsor: Health Sciences Centre, Winnipeg, Manitoba
• Collaborators: University of Manitoba; Manitoba Medical Service Foundation; Consortium of Multiple Sclerosis Centers
• Investigators: Principal Investigator: James J Marriott, MD, University of Manitoba

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: January 19, 2012
• First Submitted That Met QC Criteria: January 24, 2012
• First Posted (Estimate): January 25, 2012

Study Record Updates

• Last Update Posted (Estimate): July 8, 2014
• Last Update Submitted That Met QC Criteria: July 4, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; Fatigue
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Fatigue; Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Androgens; Anabolic Agents; Testosterone; Methyltestosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate
• Other Study ID Numbers: 38486; 812.14 (Other Grant/Funding Number: Manitoba Medical Service Foundation)