The Synergy Trial: Methylphenidate Plus a CFS-Specific Nutrient Formula as a Treatment for Chronic Fatigue Syndrome

Study Overview
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Brief Summary
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The Synergy Trial will evaluate the safety and efficacy of a currently available medication (methylphenidate hydrochloride) combined with a CFS-specific dietary supplement (CFS Nutrient Formula) to treat Chronic Fatigue Syndrome (CFS).

Detailed Description
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The Synergy Trial will evaluate the safety and efficacy of a currently available medication (methylphenidate) combined with a CFS-specific dietary supplement (CFS Nutrient Formula) to treat Chronic Fatigue Syndrome (CFS). The CFS Nutrient Formula to be used in this trial is a broad-spectrum micronutrient supplement that provides CFS patients with vitamins, minerals, and other cofactors (amino acids, antioxidants, and mitochondrial cofactors) to complement the low-dose Central Nervous System (CNS) stimulant (methylphenidate). In other words, therapeutic dosages of micronutrients are provided to support the functioning of the nervous, endocrine, and immune systems to a level at which a lower than customary dosage of methylphenidate can produce positive clinical effects on CFS symptoms and also be well tolerated. Methylphenidate is the generic form of Ritalin®. The dose being tested in this study is relatively low (5-10mg twice daily). This drug has been in clinical use for over 50 years for the treatment of Narcolepsy and Attention Deficit Disorder and has a well-described safety profile when used as recommended. Methylphenidate alone has been studied as a treatment for CFS in the past and has been shown to produce mild benefits and be well-tolerated. When provided as innovative therapy, methylphenidate plus this CFS Nutrient Formula has produced substantial improvements in CFS symptoms in a limited number of patients, and demonstrated excellent tolerability. Use of low dose methylphenidate hydrochloride coadministered with a CFS Nutrient Formula has not been previously evaluated in a controlled clinical study. The risk to patients using this combination is believed to be low, especially in the context of a well-controlled clinical study. Furthermore, this combination is not expected to increase the incidence or severity of adverse events associated with methylphenidate hydrochloride.

Official Title
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Randomized, Double-Blind, Placebo Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of Methylphenidate Hydrochloride as a Treatment for Chronic Fatigue Syndrome in Patients Taking a CFS-Specific Nutrient Formula

Conditions
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Chronic Fatigue Syndrome (CFS), Myalgic Encephalomyelitis (ME)

Intervention / Treatment
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* Drug: Methyl-P plus Nutrient Formula
* Drug: Methyl-P plus Nutrient matched placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must fulfill the 1994 CDC case definition of CFS (Fukuda et al., Ann Intern Med. 1994; 121:953-959) Subjects must also report alertness and/or concentration deficits Otherwise in good health based on medical history and screening evaluation Willingness to NOT take any nutritional or herbal supplements other than the study treatment during the course of the trial Nutritional supplements that are exempted from this requirement are limited to the following: Probiotic supplements Fiber supplements Fish oil supplements Digestive enzymes Melatonin ≤ 10mg per day Calcium ≤ 600 mg per day Magnesium ≤ 400 mg per day Vitamin D ≤ 400 i.u. per day Willingness to NOT consume any caffeine-containing supplements during the study period (coffee, tea, or chocolate are exempt). These include but are not limited to the following beverages: Red Bull® Monster® Rockstar® 5-hour® energy shots Willingness to NOT consume any pseudoephedrine-containing products during the study period Willingness to practice effective contraception Exclusion Criteria: Pregnancy or lactation Active substance abuse Major depression as defined by Zung Depression Scale score ≥ 60 Use of rintatolimod (Ampligen®) within the past 3 months Currently taking any prescription medication to treat anxiety on a daily basis Use of more than 3 times/week within the past 3 months of: Monoamine oxidase inhibitors (MAOs) Anti-psychotic medications CNS stimulants (i.e. Provigil®, Nuvigil®, Adderall®, Ritalin®, amphetamines) Narcotic opioids Tramadol (i.e. Ultram®, Ultracet®, Conzip®, or Ryzolt®) Gabapentin (Neurontin®) > 600mg/day Pregabalin (Lyrica®) Duloxetine (Cymbalta®) Milnacipran (Savella®) Coumarin anticoagulants (Coumadin®) Valganciclovir (Valcyte®) Daily concurrent use of more than one antidepressant medication except if one of the two antidepressant medications are: Amitriptyline ≤ 30mg at bedtime Trazodone ≤ 50mg at bedtime Doxepin ≤ 20mg at bedtime Active medical conditions to which treatment with methylphenidate hydrochloride or micronutrients may be contraindicated, including: Glaucoma Diabetes Mellitus Current stomach or duodenal ulcer Uncontrolled hypertension (blood pressure at screening of systolic >150 or diastolic >90) Heart disease (including cardiac arrhythmia, cardiac ischemia, syndrome of Gilles de la Tourette or a past history of myocardial infarction or cerebrovascular event) Motor tics or family history of psychosis or bipolar disorder Previous history or seizures A diagnosis of other conditions that may be in part responsible for the patient's fatigue including, but not limited to: HIV infection Chronic Hepatitis B & C Cancer (receiving treatment either currently or within the past two years) Chronic Renal Disease Clinically significant laboratory test values as determined by the Investigator Clinically significant ECG abnormalities as determined by the Medical Monitor Compliance criteria: A subject will not be eligible if he/she, in the opinion of the Investigator, will be unable to comply with any aspect of this study protocol, including the visit schedule.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Methyl-P plus Nutrient Formula<br>Methylphenidate hydrochloride plus a CFS Nutrient Formula, both taken twice daily. The CFS Nutrient Formula is a broad-spectrum CFS-specific dietary supplement that provides CFS patients with cellular fuel and cofactors (amino acids, antioxidants, and mitochondrial cofactors) while the low-dose CNS stimulant (methylphenidate hydrochloride) provides a metabolic catalyst to enhance cellular metabolism. | Drug: Methyl-P plus Nutrient Formula<br>* Week 1 (take the following together twice a day-at breakfast and lunch) One tablet of Methyl-P (5mg) Four tablets of CFS Nutrient Formula Week 2 to Week 12 (take the following together twice a day-at breakfast and lunch): Two tablets of Methyl-P (10mg) Four tablets of CFS Nutrient Formula<br>* Other names: Ritalin;|
| Placebo Comparator: Methyl-P plus Nutrient matched placebos<br>Methylphenidate matched placebo + CFS Nutrient Formula matched placebo, both taken twice daily. | Drug: Methyl-P plus Nutrient matched placebos<br>* Week 1 (take the following together twice a day-at breakfast and lunch) One tablet of Methyl-P Placebo Four tablets of CFS Nutrient Placebo Week 2 to Week 12 (take the following together twice a day-at breakfast and lunch): Two tablets of Methyl-P Placebo Four tablets of CFS Nutrient Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in patient reported Checklist Individual Strength (CIS) Total Score |  | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with 20% or greater improvement in the CIS total score |  | Week 12 | 
| Concentration Disturbances Subscore on the CIS |  | Week 12 | 
| Concentration Disturbances Score by Visual Analog Scale (VAS) |  | Week 12 | 
| Fatigue Score by Visual Analog Scale (VAS) |  | Week 12 | 
| Pain Symptoms by Brief Pain Inventory Form |  | Week 12 | 
| Patient Global Assessment of Change Questionnaires (for Fatigue and Sleep) |  | Week 12 | 
| Number of Participants with Adverse Events to Assess Safety and Tolerability |  | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Fatigue Syndrome (CFS), Myalgic Encephalomyelitis (ME), central nervous system (CNS), fatigue, alertness, brain fog, mitochondria, methylphenidate, Ritalin, stimulant, multivitamin, multimineral, micronutrients, supplements