Clinical trial NCT03186027: Coenzyme Q10 Plus NADH Supplementation in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis
Official title: Effect of Coenzyme Q10 Plus NADH Supplementation on the Changes in Fatigue Perception, Sleep Disturbances, Autonomic Function and Health-related Quality of Life in CFS/ME - A Randomized, Placebo-controlled, Double-blind Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Fatigue Syndrome
Keywords: chronic fatigue
Sleep problems
Autonomic dysfunction
Health-Related Quality of Life
Coenzyme Q10
NADH
Lead sponsor: Hospital Universitari Vall d'Hebron Research Institute
Sponsor class: OTHER
Collaborators: name: Vitae Health Innovation
First posted: 2017-06-14
Enrollment: 282
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Active Dietary Supplement: ReConnect (CoQ10 plus NADH) and excipients. ReConnect supplementation (CoQ10: 200mg/day plus NADH 20 mg/day) divided into 2 daily dose (2 tablets/ before breakfast and 2 tablets/ before lunch).

Excipient Dietary Supplement: Placebo (serine plus vitamin C) Placebo supplementation divided into two daily dose (2 tablets/before breakfast and 2 tablets/ before lunch)
Primary purpose: TREATMENT

Brief summary: The main aim of the study is to examine the effect of oral CoQ10 plus NADH (Reconnect®) supplementation twice daily for 8-weeks on the changes in fatigue perception, sleep disturbances, autonomic dysfunction and HRQoL assessed by patient-reported outcome measures in CFS/ME.

Detailed description: Chronic Fatigue Syndrome, as known as Myalgic Encephalomyelitis (CFS/ME) is a complex and extremely debilitating chronic condition, with no known cause, no established diagnostic tests, and no universal effective therapy. Its symptoms are mainly unexplained disabling fatigue that lasts for six months or more and that does not improve with rest, worsing with physical and mental activity. It is associated with other concomitant symptoms including muscle pain, post-exertional malaise lasting more than 24h, unrefreshing sleep, autonomic dysfunction and cognitive problems worsing quality of life of sufferers. Previous studies have shown that CFS/ME subjects have a significant decrease in CoQ10 and NADH levels in plasma and peripheral blood mononuclear cells (PBMCs), correlating with symptoms of the condition. Hypothesis: CoQ10 plus NADH administration could be beneficial in the improvement of outcome measures and molecular parameters in CFS/ME individuals.

A total of 282 potentially eligible Caucasian CFS/ME subjects who meet both the 1994 Centers for Disease Control and Prevention/Fukuda's definition and 2003 Canadian case criteria for CFS/ME will be initially enrolled in the study. Those patients who don't meet the inclusion criteria will excluded of the study. All participants will be treatment with ReConnect® containing CoQ10 (50 mg) plus NADH (5 mg) vs. placebo twice daily for 8-weeks in term. Scores for fatigue perception, sleep problems, autonomic dysfunction and QoL will be assess by validated questionnaires of Fatigue Impact Scale (FIS-40), Pittsburgh Sleep Quality Index (PSQI), COMPASS-31 and HRV recording device, and HRQoL (36 item Short Form Health survey), respectively.

The primary outcome is to evaluate the efficacy of oral CoQ10 plus NADH (Reconnect®) supplementation twice daily for 8-weeks on the changes in fatigue perception, sleep problems, autonomic dysfunction and health-related quality of life assessed by outcome measures in CFS/ME subjects.

The secondary outcomes are to examine the effect of oral Reconnect® administration on fatigue perception (assessed by FIS-40), sleep disruption (PSQI), autonomic function (COMPASS-31), Heart Rate Variability (HRV) for measuring R-R intervals by mobile device coupled to the Polar H7 thoracic belt and HRQoL (36-items Short Form Health survey).

Eligibility criteria: Inclusion Criteria:

1. Patients female between 18 and 65 years old.
2. Body Mass Index (BMI) ≤ 30 mg/m²
3. Subjects who met the 1994 Centers for Disease Control and Prevention/Fukuda definition and 2003 Canadian diagnostic criteria for CFS/ME.
4. Patients must be able to participate, understand and complete questionnaires in Spanish language.
5. Patients who give a signed informed consent before initiating the study.

Exclusion Criteria:

1. Patients who do not fulfilled the 1994 Centers for Disease Control and Prevention/Fukuda definition and 2003 Canadian criteria for CFS/ME.
2. Patients who are participating in another clinical trial of the same or different nature in the last 30 days prior to inclusion.
3. Any participants who, in the opinion of the principal investigator, may not be able to follow instructions or make a good treatment compliance.
4. Subjects that don't give signed informed consent to participate in the study.
5. Participants who are receiving any drug or banned substances and is expected that withdrawal of some medications/products not allowed in the study involves a significant problem.
6. Participants who are pregnant and/or breastfeeding,
7. Participants with autoimmune disorder, cancer, endocrine and metabolic disorders, rheumatic conditions, multiple sclerosis, psychosis, major depression, cardiovascular disease, hematological conditions, use of oral anticoagulants, smokers or had a history of substance abuse.

Primary outcomes:
measure: Effect of oral Reconnect ® (CoQ10 plus NADH) supplementation on the changes in core symptoms during 8-weeks in CFS/ME subjects.
timeFrame: At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
Secondary outcomes:
measure: Demographic data and clinical parameters
timeFrame: At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
measure: Age of onset of symptoms
timeFrame: At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
measure: Concomitant conditions
timeFrame: At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
measure: Height will be measured and reported
timeFrame: At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
measure: Weight will be measured and reported
timeFrame: At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
measure: Body Mass Index (BMI)
timeFrame: At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
measure: Sleep Quality
timeFrame: At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
measure: Autonomic Function
timeFrame: At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
measure: Heart Rate Variability (HRV) recording device
timeFrame: At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
measure: Health-Related Quality of Life SF36 survey
timeFrame: At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Vall d'Hebron University Hospital
Study officials:
affiliation: Vall d'Hebron University Hospital (CFS/ME Clinical Unit)
name: Jose Alegre, MD; PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Alegre J, Roses JM, Javierre C, Ruiz-Baques A, Segundo MJ, de Sevilla TF. [Nicotinamide adenine dinucleotide (NADH) in patients with chronic fatigue syndrome]. Rev Clin Esp. 2010 Jun;210(6):284-8. doi: 10.1016/j.rce.2009.09.015. Epub 2010 May 5. Spanish.
citation: Castro-Marrero J, Cordero MD, Segundo MJ, Saez-Francas N, Calvo N, Roman-Malo L, Aliste L, Fernandez de Sevilla T, Alegre J. Does oral coenzyme Q10 plus NADH supplementation improve fatigue and biochemical parameters in chronic fatigue syndrome? Antioxid Redox Signal. 2015 Mar 10;22(8):679-85. doi: 10.1089/ars.2014.6181. Epub 2014 Dec 18.
citation: Castro-Marrero J, Saez-Francas N, Segundo MJ, Calvo N, Faro M, Aliste L, Fernandez de Sevilla T, Alegre J. Effect of coenzyme Q10 plus nicotinamide adenine dinucleotide supplementation on maximum heart rate after exercise testing in chronic fatigue syndrome - A randomized, controlled, double-blind trial. Clin Nutr. 2016 Aug;35(4):826-34. doi: 10.1016/j.clnu.2015.07.010. Epub 2015 Jul 17.
citation: Castro-Marrero J, Saez-Francas N, Santillo D, Alegre J. Treatment and management of chronic fatigue syndrome/myalgic encephalomyelitis: all roads lead to Rome. Br J Pharmacol. 2017 Mar;174(5):345-369. doi: 10.1111/bph.13702. Epub 2017 Feb 1.
citation: Curriu M, Carrillo J, Massanella M, Rigau J, Alegre J, Puig J, Garcia-Quintana AM, Castro-Marrero J, Negredo E, Clotet B, Cabrera C, Blanco J. Screening NK-, B- and T-cell phenotype and function in patients suffering from Chronic Fatigue Syndrome. J Transl Med. 2013 Mar 20;11:68. doi: 10.1186/1479-5876-11-68.
citation: Castro-Marrero J, Cordero MD, Saez-Francas N, Jimenez-Gutierrez C, Aguilar-Montilla FJ, Aliste L, Alegre-Martin J. Could mitochondrial dysfunction be a differentiating marker between chronic fatigue syndrome and fibromyalgia? Antioxid Redox Signal. 2013 Nov 20;19(15):1855-60. doi: 10.1089/ars.2013.5346. Epub 2013 May 29.