Methylphenidate Plus GWI-Nutrient Formula as a Treatment for Patients With Gulf War Illness

Gulf War Illness Clinical Trial

Official title:

Phase IIa Open Label Study to Evaluate the Safety, Tolerability, and Efficacy of KPAX 002 (Methylphenidate Hydrochloride + K-PAX Synergy) as a Treatment for Gulf War Illness in Patients Meeting the Kansas Case Definition

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02357030
• Other study ID #: K-PAX-002-2
• Secondary ID: CDMRP- GW130047
• Status: Recruiting
• Phase: Phase 2
• First received: January 25, 2015
• Last updated: October 13, 2015
• Start date: January 2015
• Est. completion date: May 2016

Study information

• Verified date: October 2015
• Source: K-PAX Pharmaceuticals, Inc.
• Contact: Jessica Lopez
• Phone: (650) 493-5000
• Email: jessica.lopez[@]va.gov
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The Gulf War Synergy Trial will evaluate the safety and efficacy of a currently available medication, methylphenidate (Ritalin®), combined with a GWI Nutrient Formula (K-PAX Synergy) to treat Gulf War Illness (GWI).

Description:

This trial will evaluate the safety and efficacy of a currently available medication, methylphenidate (Ritalin®), combined with a mitochondrial support nutrient formula (K-PAX Synergy) to treat Gulf War Illness (GWI).

The nutrient formula to be used in this trial is a broad-spectrum micronutrient supplement. This nutrient formula provides GWI patients with vitamins, minerals, and other cofactors (amino acids, antioxidants, and mitochondrial cofactors) to complement the low-dose Central Nervous System (CNS) stimulant (methylphenidate). The low-dose CNS stimulant provides the necessary catalyst to augment the metabolism of cellular fuel and the production of cellular energy.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 GWI symptoms and also be well tolerated without further depleting or degrading these systems.

The dose of methylphenidate (Ritalin®) 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. GWI and Chronic Fatigue Syndrome (CFS) share a high degree of symptom overlap. They have both been linked to mitochondrial dysfunction. 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 coadministered with a mitochondria support 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: May 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 64 Years

Eligibility

1. Male and female patients between the ages of 18 and 64, inclusive at the time of informed consent

2. Patients who currently meet the Kansas Case Definition for GWI

3. Patients who are otherwise in good health based on medical history and screening evaluation as determined by Investigator (see below for specific exclusion criteria)

4. Willingness to not take any multivitamin, nutritional or herbal supplements other than the study treatment during the course of the trial; at least a one week washout of current nutritional supplements will be required between the screening and baseline visits. Nutritional supplements that are exempted from this requirement are limited to the following (other exemptions require a waiver by the Medical Monitor):

1. Probiotic supplements (L. acidophilus, Bifidobacterium, etc.)

2. Fiber supplements

3. Fish oil supplements

4. Digestive enzymes

5. Melatonin < 10mg per day

6. Calcium < 600mg per day

7. Magnesium < 400mg per day

8. Vitamin D < 400 i.u. per day

5. Willingness to not consume any caffeine-containing supplements during the study period (coffee, tea and chocolate are exempt). These supplements include but are not limited to the following:

1. Red Bull®

2. Monster®

3. Rockstar®

4. 5-hour® energy shots

6. Willingness to not consume any prescription stimulants (i.e. Provigil®, Nuvigil®, Adderall®, Ritalin®, amphetamines) during the study period.

7. Willingness to not consume any pseudoephedrine-containing products during the study period.

8. Willingness of females to practice effective contraception.

Exclusion Criteria:

1. Pregnancy or lactation

2. Active substance or alcohol abuse and/or a history of prescription stimulant abuse

3. Hospitalization within the past five years for any of the following:

1. Active substance or alcohol abuse and/or a history of prescription stimulant abuse

2. Major Depressive Disorder (MDD)

3. Post Traumatic Stress Disorder (PTSD)

4. Previous or current diagnosis of schizophrenia or bipolar disorder

5. Currently taking any prescription medication to treat anxiety on a daily basis

6. Use of any of the below medications more than 3 times per week within the past 3 months:

1. MAO inhibitors

2. Anti-psychotic medications

3. Prescription stimulants (i.e. Provigil®, Nuvigil®, Adderall®, Ritalin®, or any other amphetamines)

4. Coumarin anticoagulants (Coumadin®)

7. Daily concurrent use of more than one antidepressant medication except if one of the two antidepressant medications are one of the following (unless specifically granted a waiver by the Medical Monitor):

1. Amitriptyline = 100 qhs

2. Trazodone = 100 qhs

3. Doxepin = 50 qhs

8. Active medical conditions including:

1. Glaucoma

2. Diabetes mellitus

3. Current stomach or duodenal ulcer

4. Uncontrolled hypertension (blood pressure at screening of systolic >160 or diastolic >90)

5. Heart disease (including a history of cardiac arrhythmia, cardiac ischemia, syndrome of Torsade de Pointes, myocardial infarction or cerebrovascular event)

6. Motor tics or a diagnosis or family history of Tourette's syndrome

7. Previous history of seizures

8. A diagnosis of any of the following conditions:

• Cancer (receiving systemic treatment either currently or within the past 12 months)

• Chronic Renal Disease

• Chronic Liver Disease

• HIV Infection

• Chronic Hepatitis B or C

• Systemic Lupus Erythematosus

• Multiple Sclerosis

• Rheumatoid Arthritis

• Parkinson's Disease

• Amyotrophic Lateral Sclerosis (ALS)

• Any chronic infectious disease lasting six months or longer

9. Clinically significant laboratory test values as determined by the Medical Monitor

10. Clinically significant ECG abnormalities as determined by the Medical Monitor

11. The taking of another investigational treatment either currently or within 30 days of the screening visit

12. 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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Gulf War Illness

Intervention

Drug:
• Methyl-P plus GWI Nutrient Formula
Week 1: One tablet of Methyl-P (5mg) twice daily Four tablets of GWI Nutrient Formula twice daily Week 2 to Week 12 : Two tablets of Methyl-P (10mg) twice daily Four tablets of GWI Nutrient Formula twice daily

Locations

Country	Name	City	State
United States	Veterans Administration Palo Alto Health Care System (VAPAHCS)	Palo Alto	California

Sponsors (2)

Lead Sponsor	Collaborator
K-PAX Pharmaceuticals, Inc.	VA Palo Alto Health Care System

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in patient reported Checklist Individual Strength (CIS) total score		Week 12	No
Secondary	Percentage of patients with 20% or greater improvement in the CIS total score		Week 12	No
Secondary	Concentration Disturbances Subscore on the CIS		Week 12	No
Secondary	Concentration Disturbances Score by Visual Analog Scale (VAS)		Week 12	No
Secondary	Fatigue Score by Visual Analog Scale (VAS)		Week 12	No
Secondary	Pain Score by Visual Analog Scale (VAS)		Week 12	No
Secondary	Sleep Score by Visual Analog Scale (VAS)		Week 12	No
Secondary	Mitochondrial Function Assays		Week 12	No
Secondary	GWI Symptoms Assessment Tool (SAT) Score		Week 12	No
Secondary	Number of Participants with Adverse Events to Assess Safety and Tolerability		Week 12	No