Coenzyme Q10 Plus NADH Supplementation in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CONNeCT)
Primary Purpose
Chronic Fatigue Syndrome
Status
Completed
Phase
Not Applicable
Locations
Spain
Study Type
Interventional
Intervention
Coenzyme Q10 plus NADH
phosphoserine plus vitamin C
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Fatigue Syndrome focused on measuring chronic fatigue, Sleep problems, Autonomic dysfunction, Health-Related Quality of Life, Coenzyme Q10, NADH
Eligibility Criteria
Inclusion Criteria:
- Patients female between 18 and 65 years old.
- Body Mass Index (BMI) ≤ 30 mg/m²
- Subjects who met the 1994 Centers for Disease Control and Prevention/Fukuda definition and 2003 Canadian diagnostic criteria for CFS/ME.
- Patients must be able to participate, understand and complete questionnaires in Spanish language.
- Patients who give a signed informed consent before initiating the study.
Exclusion Criteria:
- Patients who do not fulfilled the 1994 Centers for Disease Control and Prevention/Fukuda definition and 2003 Canadian criteria for CFS/ME.
- Patients who are participating in another clinical trial of the same or different nature in the last 30 days prior to inclusion.
- Any participants who, in the opinion of the principal investigator, may not be able to follow instructions or make a good treatment compliance.
- Subjects that don't give signed informed consent to participate in the study.
- 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.
- Participants who are pregnant and/or breastfeeding,
- 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.
Sites / Locations
- Vall d'Hebron University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Active supplement (CoQ10 plus NADH)
Phosphoserine plus vitamin C
Arm Description
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
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
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
Demographic data and clinical parameters
Sex
Age of onset of symptoms
Age at onset of fatigue
Concomitant conditions
Comorbid illnesses associated with ME/CFS
Height will be measured and reported
Height in meters
Weight will be measured and reported
Weight in kilograms
Body Mass Index (BMI)
Height and Weight will be combined to report BMI in kg/m^2
Sleep Quality
Pittsburgh Quality of Sleep Index (18 items) for non-refreshing sleep
Autonomic Function
COMPASS-31 Questionnaire (31-items) to assess autonomic dysfunction
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).
Health-Related Quality of Life SF36 survey
Short Form-36 Health Survey (36-items) to measure quality of life of participants.
Full Information
NCT ID
NCT03186027
First Posted
May 24, 2017
Last Updated
September 19, 2022
Sponsor
Hospital Universitari Vall d'Hebron Research Institute
Collaborators
Vitae Health Innovation
1. Study Identification
Unique Protocol Identification Number
NCT03186027
Brief Title
Coenzyme Q10 Plus NADH Supplementation in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis
Acronym
CONNeCT
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
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Completed
Study Start Date
June 28, 2017 (Actual)
Primary Completion Date
May 28, 2020 (Actual)
Study Completion Date
September 1, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospital Universitari Vall d'Hebron Research Institute
Collaborators
Vitae Health Innovation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Fatigue Syndrome
Keywords
chronic fatigue, Sleep problems, Autonomic dysfunction, Health-Related Quality of Life, Coenzyme Q10, NADH
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
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)
Masking
ParticipantCare ProviderInvestigator
Masking Description
The investigator, care provider and participants do not know which individuals have been assigned in each arm or comparison group.
Allocation
Randomized
Enrollment
282 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Active supplement (CoQ10 plus NADH)
Arm Type
Active Comparator
Arm Description
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
Arm Title
Phosphoserine plus vitamin C
Arm Type
Placebo Comparator
Arm Description
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
Intervention Type
Dietary Supplement
Intervention Name(s)
Coenzyme Q10 plus NADH
Intervention Description
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
Intervention Type
Dietary Supplement
Intervention Name(s)
phosphoserine plus vitamin C
Intervention Description
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
Primary Outcome Measure Information:
Title
Effect of oral Reconnect ® (CoQ10 plus NADH) supplementation on the changes in core symptoms during 8-weeks in CFS/ME subjects.
Description
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).
Time Frame
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 Measure Information:
Title
Demographic data and clinical parameters
Description
Sex
Time Frame
At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
Title
Age of onset of symptoms
Description
Age at onset of fatigue
Time Frame
At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
Title
Concomitant conditions
Description
Comorbid illnesses associated with ME/CFS
Time Frame
At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
Title
Height will be measured and reported
Description
Height in meters
Time Frame
At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
Title
Weight will be measured and reported
Description
Weight in kilograms
Time Frame
At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
Title
Body Mass Index (BMI)
Description
Height and Weight will be combined to report BMI in kg/m^2
Time Frame
At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
Title
Sleep Quality
Description
Pittsburgh Quality of Sleep Index (18 items) for non-refreshing sleep
Time Frame
At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
Title
Autonomic Function
Description
COMPASS-31 Questionnaire (31-items) to assess autonomic dysfunction
Time Frame
At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
Title
Heart Rate Variability (HRV) recording device
Description
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).
Time Frame
At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
Title
Health-Related Quality of Life SF36 survey
Description
Short Form-36 Health Survey (36-items) to measure quality of life of participants.
Time Frame
At the beginning (session 2, week 1), intermedium stage (session 3, week 4) and at the close-up of study (session 4, week 8)
10. Eligibility
Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients female between 18 and 65 years old.
Body Mass Index (BMI) ≤ 30 mg/m²
Subjects who met the 1994 Centers for Disease Control and Prevention/Fukuda definition and 2003 Canadian diagnostic criteria for CFS/ME.
Patients must be able to participate, understand and complete questionnaires in Spanish language.
Patients who give a signed informed consent before initiating the study.
Exclusion Criteria:
Patients who do not fulfilled the 1994 Centers for Disease Control and Prevention/Fukuda definition and 2003 Canadian criteria for CFS/ME.
Patients who are participating in another clinical trial of the same or different nature in the last 30 days prior to inclusion.
Any participants who, in the opinion of the principal investigator, may not be able to follow instructions or make a good treatment compliance.
Subjects that don't give signed informed consent to participate in the study.
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.
Participants who are pregnant and/or breastfeeding,
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jose Alegre, MD; PhD
Organizational Affiliation
Vall d'Hebron University Hospital (CFS/ME Clinical Unit)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vall d'Hebron University Hospital
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
20447621
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.
Results Reference
result
PubMed Identifier
25386668
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.
Results Reference
result
PubMed Identifier
26212172
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.
Results Reference
result
PubMed Identifier
28052319
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.
Results Reference
result
PubMed Identifier
23514202
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.
Results Reference
result
PubMed Identifier
23600892
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.
Results Reference
result
Links:
URL
http://www.vhir.org
Description
Vall d'Hebron University Hospital Research Institute (VHIR)
URL
http://www.vhebron.net
Description
Vall d'Hebron University Hospital (HUVH)
Learn more about this trial
Coenzyme Q10 Plus NADH Supplementation in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis
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