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

K-PAX Pharmaceuticals

Status and phase: Unknown; Phase 2

Conditions: Myalgic Encephalomyelitis (ME); Chronic Fatigue Syndrome (CFS)

Treatments: Drug: Methyl-P plus Nutrient matched placebos; Drug: Methyl-P plus Nutrient Formula

Study type: Interventional

Funder types: Industry

Identifiers

NCT01966276

KPAX-002-01

Details and patient eligibility

About

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).

Full 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.

Enrollment: 134 patients

Sex: All

Ages: 18 to 59 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

134 participants in 2 patient groups, including a placebo group

Methyl-P plus Nutrient Formula

Experimental group

Description:

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.

Treatment:

Drug: Methyl-P plus Nutrient Formula

Methyl-P plus Nutrient matched placebos

Placebo Comparator group

Description:

Methylphenidate matched placebo + CFS Nutrient Formula matched placebo, both taken twice daily.

Treatment:

Drug: Methyl-P plus Nutrient matched placebos