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

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

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).

Study Overview

• Status: Unknown
• Conditions: Chronic Fatigue Syndrome (CFS); Myalgic Encephalomyelitis (ME)
• Intervention / Treatment: Drug: Methyl-P plus Nutrient Formula; Drug: Methyl-P plus Nutrient matched placebos

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 134
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford Chronic Fatigue Syndrome/ME Initiative
  • Florida
    • Fort Lauderdale, Florida, United States, 33328
      • Nova Southeastern University
  • New York
    • New York, New York, United States, 10021
      • Susan Levine, MD
  • Utah
    • Salt Lake City, Utah, United States, 84102
      • Fatigue Consultation Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 59 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Methyl-P plus Nutrient Formula; 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; 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; Other Names: Ritalin
Placebo Comparator: Methyl-P plus Nutrient matched placebos; Methylphenidate matched placebo + CFS Nutrient Formula matched placebo, both taken twice daily.	Drug: Methyl-P plus Nutrient matched placebos; Week 1 (take the following together twice a day-at breakfast and lunch)One tablet of Methyl-P PlaceboFour 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 PlaceboFour tablets of CFS Nutrient Placebo

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: K-PAX Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Jose Montoya, M.D., Stanford University School of Medicine, Division of Infectious Diseases

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Anticipated): December 1, 2014
• Study Completion (Anticipated): December 1, 2014

Study Registration Dates

• First Submitted: October 14, 2013
• First Submitted That Met QC Criteria: October 16, 2013
• First Posted (Estimate): October 21, 2013

Study Record Updates

• Last Update Posted (Estimate): September 25, 2014
• Last Update Submitted That Met QC Criteria: September 22, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: fatigue; mitochondria; micronutrients; supplements; stimulant; Ritalin; Myalgic Encephalomyelitis (ME); alertness; methylphenidate; brain fog; Chronic Fatigue Syndrome (CFS); central nervous system (CNS); multivitamin; multimineral
• Additional Relevant MeSH Terms: Pathologic Processes; Central Nervous System Diseases; Nervous System Diseases; Virus Diseases; Infections; Pain; Neurologic Manifestations; Disease; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Musculoskeletal Pain; Central Nervous System Infections; Syndrome; Fatigue; Myalgia; Fatigue Syndrome, Chronic; Encephalomyelitis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Methylphenidate
• Other Study ID Numbers: KPAX-002-01