Coenzyme Q10 Plus NADH Supplementation in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CONNeCT)

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.

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.

Study Overview

• Status: Completed
• Conditions: Chronic Fatigue Syndrome
• Intervention / Treatment: Dietary supplement: Coenzyme Q10 plus NADH; Dietary supplement: phosphoserine plus vitamin C

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).

• Study Type: Interventional
• Enrollment (Actual): 282
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08035
    • Vall d'Hebron University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

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
Active Comparator: Active supplement (CoQ10 plus NADH); CFS/ME patients will be randomized to evaluate the effect of oral ReConnect supplementation (CoQ10: 200 mg/day plus NADH: 20 mg/day) taking 4 tablets/day during 8-weeks in term. Active supplement based on Coenzyme Q10 plus NADH	Dietary supplement: Coenzyme Q10 plus NADH; Active arm: Coenzyme Q10 plus NADH CFS/ME patients who will be randomized to measure the effect of oral ReConnect supplementation (CoQ10: 200 mg/day plus NADH 20 mg/day; 4 tablets/day) on changes in the fatigue, sleep problems, autonomic function and HRQoL during 8-weeks in term. Intervention: Reconnect
Placebo Comparator: Phosphoserine plus vitamin C; CFS/ME patients will be randomized to assess the effect of placebo (phospho-serine plus vitamin C) taking 4 tablets/day for 8-weeks in term. Placebo: phosphoserine plus vitamin C	Dietary supplement: phosphoserine plus vitamin C; Placebo arm: phosphoserine plus vitamin C CFS/ME patients who will be randomized to measure the effect of oral Placebo supplementation (phosphoserine and vit C, 4 tablets/day) on changes in the fatigue, sleep problems, autonomic function and HRQoL during 8-weeks in term. Intervention: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of oral Reconnect ® (CoQ10 plus NADH) supplementation on the changes in core symptoms during 8-weeks in CFS/ME subjects.	Evaluate the effect of oral Reconnect ® supplementation on the changes in fatigue perception measured by the Fatigue Index Scale-40 (40 items) in all study participants. Items Rate: 0 (no fatigue) to 4 (severe fatigue).	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Demographic data and clinical parameters	Sex	At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
Age of onset of symptoms	Age at onset of fatigue	At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
Concomitant conditions	Comorbid illnesses associated with ME/CFS	At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
Height will be measured and reported	Height in meters	At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
Weight will be measured and reported	Weight in kilograms	At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
Body Mass Index (BMI)	Height and Weight will be combined to report BMI in kg/m^2	At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
Sleep Quality	Pittsburgh Quality of Sleep Index (18 items) for non-refreshing sleep	At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
Autonomic Function	COMPASS-31 Questionnaire (31-items) to assess autonomic dysfunction	At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
Heart Rate Variability (HRV) recording device	Time domain - NN (normal-to-normal R-R interval), HRV index (total number of all NN/ the height of the histogram of all NN), SDNN (standard deviation of the NN), RMSSD (the root mean square of differences of successive NN), NN50 (number of pairs of adjacent NN intervals differing by more than 50 ms in the entire recording) and pNN50(NN50/total number of all NN). Frequency domain - TP (the variance of NN intervals over the temporal segment), VLF(power in very low frequency range; < 0.04 Hz), LF (Power in low frequency range; 0.04~0.15 Hz), HF(Power in high frequency range; 0.15~0.4 Hz).	At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
Health-Related Quality of Life SF36 survey	Short Form-36 Health Survey (36-items) to measure quality of life of participants.	At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)

Collaborators and Investigators

• Sponsor: Hospital Universitari Vall d'Hebron Research Institute
• Collaborators: Vitae Health Innovation
• Investigators: Principal Investigator: Jose Alegre, MD; PhD, Vall d'Hebron University Hospital (CFS/ME Clinical Unit)

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Helpful Links

• Vall d'Hebron University Hospital Research Institute (VHIR)
• Vall d'Hebron University Hospital (HUVH)

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2017
• Primary Completion (Actual): May 28, 2020
• Study Completion (Actual): September 1, 2021

Study Registration Dates

• First Submitted: May 24, 2017
• First Submitted That Met QC Criteria: June 11, 2017
• First Posted (Actual): June 14, 2017

Study Record Updates

• Last Update Posted (Actual): September 21, 2022
• Last Update Submitted That Met QC Criteria: September 19, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: NADH; Coenzyme Q10; Sleep problems; Autonomic dysfunction; chronic fatigue; Health-Related Quality of Life
• Additional Relevant MeSH Terms: Pathologic Processes; Central Nervous System Diseases; Nervous System Diseases; Virus Diseases; Infections; Disease; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Encephalomyelitis; Syndrome; Fatigue; Fatigue Syndrome, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Ascorbic Acid; Coenzyme Q10; Ubiquinone
• Other Study ID Numbers: VITAE 2015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No