Chronic Fatigue SyndromeMelatoZincMENCT05454683
Melatonin and Zinc Administration on Cardinal Symptoms in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
A study testing melatonin plus zinc and isomaltose and magnesium stearate in people with Chronic Fatigue Syndrome and Myalgic Encephalomyelitis, run by Laboratorios Viñas, S.A. at 1 site in Spain.
Trial summary
The aim of the study is to investigate the effects of oral melatonin and zinc supplementation on core features in individuals with ME/CFS Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Chronic Fatigue Syndrome, Myalgic Encephalomyelitis
- What is being tested?
- melatonin plus zinc and isomaltose and magnesium stearate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 106 participants
- Where
- 1 siteSpain
- Study dates
- 5 Sep 2022to 31 Dec 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients between 18 and 65 years of age.
- Patients with ME/CFS who met the diagnostic criteria (2011 ICC criteria) from the Central Sensitization Syndrome Unit (USSC) at the Vall d'Hebron University Hospital.
- Patients who freely give written consent.
Who cannot join
- Any active medical condition that explained chronic fatigue (untreated hypothyroidism, sleep apnea, narcolepsy, medication side-effects).
- Previous diagnosis not unequivocally resolved (chronic hepatitis, malignancy).
- Past or current psychiatric disorders (major depressive disorder with psychotic or melancholic features, bipolar disorder, schizophrenia, delusional disorder, dementias, anorexia nervosa, bulimia nervosa).
- Participation in another clinical trial of the same or different nature in the 30 days prior to study inclusion.
- In the judgment of the investigator, inability to follow the instructions or to complete the treatment satisfactorily.
- Failure to provide signed informed consent.
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- Current consumption of medications that may interfere with the results and/or whose withdrawal may be a relevant problem.
- Anticoagulant treatment.
- Pregnancy or breast-feeding, or had not used oral contraceptives or other hormonal preparations in the previous 6 months.
- Smoking, alcohol intake or substance abuse.
- Severe obesity (class 3 BMI ≥ 40 kg/m2).
- Hypersensitivity to melatonin and/or zinc dietary supplements.
Trial locations and contacts
1 site in 1 country.
Spain1 site, 1 recruiting
- Recruiting
Vall d'Hebron University Hospital
Barcelona, 08035
José Alegre, MD; PhD, +34934893000 ext. 4927, jalegre@vhebron.net
Jesús Castro, PhD, +34934893000 ext. 4927, jesus.castro@vhir.org
About this study
Official title: Effect of Melatonin Plus Zinc Supplementation on Fatigue, Pain, Sleep Disturbances, Anxiety and Depression, and Autonomic Dysfunction in ME/CFS: a Randomized, Double-blind, Placebo-controlled Study
The aim of the study is to investigate the effects of oral melatonin and zinc supplementation on core features in individuals with ME/CFS
Read the detailed description
Myalgic Encephalomyelitis, also known as Chronic Fatigue Syndrome (ME/CFS) is a heterogeneous condition characterized mainly by debilitating and prolonged fatigue, post-exertional malaise (physical, mental and emotional), unrefreshing sleep, cognitive impairment, and orthostatic intolerance with prolonged recovery that is not relieved by rest. Currently, the etiopathogenic mechanisms of ME/CFS are unknown. At present, there is no diagnostic test or effective treatment. MelatoZinc is a food supplement composed of melatonin and zinc, which could contribute to the circadian rhythm homeostasis and regulation of redox imbalance and immune response.
The aim is to evaluate the efficacy and safety of oral treatment with MelatoZinc on the symptomatic complex of fatigue in a larger Spanish ME/CFS population.
This is a single-center, randomized, double-blind, placebo controlled clinical trial. It will include a total of 106 ME/CFS patients who met 2011 ICC criteria for ME/CFS. All patients will take one capsule daily for 16 weeks. Group A will receive MelatoZinc (1 mg melatonin plus 10 mg zinc), and group B will receive a placebo (excipients: isomaltose and magnesium stearate). Clinical symptoms will be evaluated, and standardized questionnaires will be applied to assess the impact of fatigue, pain, anxiety-depression symptoms, sleep quality, dysautonomia, and quality of life. Heart rate variability (HRV) and orthostatic intolerance (10-min NASA Lean Test) will be performed to evaluate autonomic dysfunction. Sleep efficiency will be estimated through an actigraph sensor
- Being tested
- melatonin plus zinc, isomaltose and magnesium stearate
- Keywords
- melatonin, zinc, fatigue, sleep quality, quality of life, pain, anxiety and depression, actigraphy, heart rate variability, orthostatic intolerance
- Medical subject headings
- Fatigue Syndrome, Chronic, Fatigue, Sleep Initiation and Maintenance Disorders, Pain, Anxiety Disorders, Depression, Orthostatic Intolerance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
melatonin plus zincDietary supplement
Also called MelatoZinc
One capsule with melatonin 1mg plus zinc 10 mg o.d. 30 minutes before bedtime, at least 1 hour after dinner during 4 months
isomaltose and magnesium stearateOther
Also called excipients
One capsule with excipients o.d. 30 minutes before bedtime, at least 1 hour after dinner during 4 months
| Study group | Role | What they receive |
|---|---|---|
| Melatonin plus Zinc | Experimental | Dietary Supplement:
53 patients treated with melatonin 1 mg plus Zinc 10 mg Receives: Dietary Supplement: melatonin plus zinc |
| Placebo | Placebo comparator | 53 patients treated with isomaltose and magnesium stearate (excipients) Receives: Other: isomaltose and magnesium stearate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Self-reported fatigue as assessed by the 40-item Fatigue Impact Scale (FIS-40) over the baseline in the study participants.
The FIS-40 includes three subscales of the perceived impact of fatigue: cognitive (10 items), physical (10 items) and psychosocial functions (20 items), each item being scored from 0 (no fatigue) to 4 (severe fatigue). The total score is calculated by adding together the responses from the 40 questions (range 0-160). Higher scores indicate more functional limitations due to fatigue.
Measured: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
Secondary outcomes (14)
The health-related quality of life (HRQoL) as assessed by the Short-Form 36-Item Health Survey (SF-36) over the baseline in the study participants.
The SF-36 is a broadly-based self-reported survey on health-related physical and mental functioning status. It assesses functioning on eight subscales, including domains of physical functioning, physical role, bodily pain, general health, social functioning, vitality, emotional role and mental health, and two general subscales covering the physical and mental health domains on a 0-100 score. Lower scores indicate a more negative impact of an individual's health on functioning.
Measured: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
Sleep disturbances as assessed by the Pittsburgh Sleep Quality Index (PSQI) questionnaire over the baseline in the study participants.
The PSQI is the self-administered 19-item questionnaire. PSQI scores are obtained on each of seven components of sleep quality: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep perturbations, use of sleeping medication and daytime dysfunction. Each item is scored from 0 to 3 (0 = no sleep problems and 3 = severe sleep problems). The global PSQI score ranges from 0 to 21 points, with scores of >5 indicating poorer sleep quality.
Measured: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
Sleepiness as assessed by the Epworth Sleepiness Scale (ESS) over the baseline in the study participants.
The ESS is a short, self-administered questionnaire that consists of eight questions asking to rate how likely it is to fall asleep in everyday situations (each question can be scored from 0 to 3 points: '0' indicates no sleepiness, and '3' indicates significant sleepiness). It provides a total score which has been shown to relate to the subject's level of daytime sleepiness (total score is ranging from 0 to 24 points).
Measured: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
Sleep latency as assessed by an actigraph sensor over the baseline in the study participants.
An actigraph (Actiwatch Spectrum Plus® from Philips Respironics, Linton Instrumentation, UK) on the wrist of the non-dominant arm is continuously recording for seven days. The same device was programmed to collect data on motor activity (accelerometer) and light type/intensity (lux) at one minute intervals. These variables were recorded and stored in the device's memory for data analysis.
Measured: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
Sleep onset as assessed by an actigraph sensor over the baseline in the study participants
An actigraph (Actiwatch Spectrum Plus® from Philips Respironics, Linton Instrumentation, UK) on the wrist of the non-dominant arm is continuously recording for seven days. The same device is programmed to collect data on motor activity (accelerometer) and light type/intensity (lux) at one minute intervals. These variables will be recorded and stored in the device's memory for further data analysis.
Measured: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
Sleep efficiency as assessed by an actigraph sensor over the baseline in the study participants.
An actigraph (Actiwatch Spectrum Plus® from Philips Respironics, Linton Instrumentation, UK) on the wrist of the non-dominant arm is continuously recording for seven days. The same device is programmed to collect data on motor activity (accelerometer) and light type/intensity (lux) at one minute intervals. These variables will be recorded and stored in the device's memory for further data analysis.
Measured: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
Total sleep time as assessed by an actigraph sensor over the baseline in the study participants.
An actigraph (Actiwatch Spectrum Plus® from Philips Respironics, Linton Instrumentation, UK) on the wrist of the non-dominant arm is continuously recording for seven days. The same device is programmed to collect data on motor activity (accelerometer) and light type/intensity (lux) at one minute intervals. These variables will be recorded and stored in the device's memory for further data analysis.
Measured: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
Wake time as assessed by an actigraph sensor over the baseline in the study participants.
An actigraph (Actiwatch Spectrum Plus® from Philips Respironics, Linton Instrumentation, UK) on the wrist of the non-dominant arm is continuously recording for seven days. The same device is programmed to collect data on motor activity (accelerometer) and light type/intensity (lux) at one minute intervals. These variables will be recorded and stored in the device's memory for further data analysis.
Measured: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
Number of awakenings as assessed by an actigraph sensor over the baseline in the study participants.
An actigraph (Actiwatch Spectrum Plus® from Philips Respironics, Linton Instrumentation, UK) on the wrist of the non-dominant arm is continuously recording for seven days. The same device is programmed to collect data on motor activity (accelerometer) and light type/intensity (lux) at one minute intervals. These variables will be recorded and stored in the device's memory for further data analysis.
Measured: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
Heart rate variability (HRV) as recorded by the FitLab software over the baseline in the study participants.
Changes in the cardiovagal autonomic dysfuntion will be continuously assessed and recorded for the R-R intervals over 5-min periods at rest and in the supine position on different days using the FitLab software.
Measured: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
Orthostatic intolerance as assessed by the active standing test (10-minute NASA Lean test) over the baseline in the study participants.
The 10-minute NLT is a well-established non-invasive procedure used to assess impaired cardiovascular responses to standing and to diagnose OI phenotypes. It records objective hemodynamic parameters (blood pressure and heart rate). The participants will be first asked to lie down during 5 minutes and then to stand and lean against a wall, with heels 6-8 inches from the wall. Throughout the recording, participants will be asked to remain motionless, quiet and any talking or movement will be discouraged, except for reporting any symptoms of concern.
Measured: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
Pain intensity as assessed by a visual analog scale (VAS) over the baseline in the study participants.
The pain VAS is a continuous and unidimensional measure of pain intensity. It comprised of a horizontal line of 10-centimeters in length, anchored by 2 verbal descriptors, one for each symptom extreme. "No pain" (score of 0) and "pain as bad as it could be" or "worst imaginable pain"(score of 10).
Measured: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
Anxiety and depression symptoms as assessed by the Hospital Anxiety and Depression Scale (HADS) over the baseline in the study participants.
The HADS is a validated self-reported tool composed of 14 items (seven related to anxiety symptoms and seven to depression). Each item is scored from 0-3, and thus, scores range from 0 to 21; scores of 0-7 are interpreted as normal, 8-10 as mild, 11-14 as moderate, and 15-21 as severe for either anxiety or depression. The total HADS score ranges from 0 (no anxiety or depression) to 42 (severe anxiety and depression).
Measured: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
Side effect of treatment
Treatment side effects will be collected from each participant during clinical trial.
Measured: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2022
- Study start5 Sep 2022 (estimated)
- Primary completion30 Sep 2024 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (27)Papers the sponsor has linked to this study.
- Other trials for Chronic Fatigue SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 106 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Laboratorios Viñas, S.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Laboratorio Echevarne, Hospital Vall d'Hebron
- Responsible party
- Sponsor
- Investigators
- José Alegre, MD, PhD, Principal investigator, Vall d'Hebron University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05454683
- Sponsor's protocol ID
- IC/LV/MEL-ZN/SFC2
- Acronym
- MelatoZincME
- Status last verified
- Jul 2022
- First submitted
- 30 Jun 2022
- Last updated
- 12 Jul 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Castro-Marrero J, Zaragoza MC, Lopez-Vilchez I, Galmes JL, Cordobilla B, Maurel S, Domingo JC, Alegre-Martin J. Effect of Melatonin Plus Zinc Supplementation on Fatigue Perception in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial. Antioxidants (Basel). 2021 Jun 23;10(7):1010. doi: 10.3390/antiox10071010.
PubMed 34201806Castro-Marrero J, Domingo JC, Cordobilla B, Ferrer R, Giralt M, Sanmartin-Sentanes R, Alegre-Martin J. Does Coenzyme Q10 Plus Selenium Supplementation Ameliorate Clinical Outcomes by Modulating Oxidative Stress and Inflammation in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome? Antioxid Redox Signal. 2022 Apr;36(10-12):729-739. doi: 10.1089/ars.2022.0018.
PubMed 35229657Castro-Marrero J, Zacares M, Almenar-Perez E, Alegre-Martin J, Oltra E. Complement Component C1q as a Potential Diagnostic Tool for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Subtyping. J Clin Med. 2021 Sep 15;10(18):4171. doi: 10.3390/jcm10184171.
PubMed 34575280Castro-Marrero J, Segundo MJ, Lacasa M, Martinez-Martinez A, Sentanes RS, Alegre-Martin J. Effect of Dietary Coenzyme Q10 Plus NADH Supplementation on Fatigue Perception and Health-Related Quality of Life in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients. 2021 Jul 30;13(8):2658. doi: 10.3390/nu13082658.
PubMed 34444817Baklund IH, Dammen T, Moum TA, Kristiansen W, Duarte DS, Castro-Marrero J, Helland IB, Strand EB. Evaluating Routine Blood Tests According to Clinical Symptoms and Diagnostic Criteria in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. J Clin Med. 2021 Jul 14;10(14):3105. doi: 10.3390/jcm10143105.
PubMed 34300271Capdevila L, Castro-Marrero J, Alegre J, Ramos-Castro J, Escorihuela RM. Analysis of Gender Differences in HRV of Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Using Mobile-Health Technology. Sensors (Basel). 2021 May 28;21(11):3746. doi: 10.3390/s21113746.
PubMed 34071326Domingo JC, Cordobilla B, Ferrer R, Giralt M, Alegre-Martin J, Castro-Marrero J. Are Circulating Fibroblast Growth Factor 21 and N-Terminal Prohormone of Brain Natriuretic Peptide Promising Novel Biomarkers in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome? Antioxid Redox Signal. 2021 Jun 20;34(18):1420-1427. doi: 10.1089/ars.2020.8230. Epub 2021 Feb 11.
PubMed 33353469Gomez-Mora E, Carrillo J, Urrea V, Rigau J, Alegre J, Cabrera C, Oltra E, Castro-Marrero J, Blanco J. Impact of Long-Term Cryopreservation on Blood Immune Cell Markers in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Implications for Biomarker Discovery. Front Immunol. 2020 Nov 17;11:582330. doi: 10.3389/fimmu.2020.582330. eCollection 2020.
PubMed 33329554Giloteaux L, O'Neal A, Castro-Marrero J, Levine SM, Hanson MR. Cytokine profiling of extracellular vesicles isolated from plasma in myalgic encephalomyelitis/chronic fatigue syndrome: a pilot study. J Transl Med. 2020 Oct 12;18(1):387. doi: 10.1186/s12967-020-02560-0.
PubMed 33046133Estevez-Lopez F, Mudie K, Wang-Steverding X, Bakken IJ, Ivanovs A, Castro-Marrero J, Nacul L, Alegre J, Zalewski P, Slomko J, Strand EB, Pheby D, Shikova E, Lorusso L, Capelli E, Sekulic S, Scheibenbogen C, Sepulveda N, Murovska M, Lacerda E. Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology. J Clin Med. 2020 May 21;9(5):1557. doi: 10.3390/jcm9051557.
PubMed 32455633Cheema AK, Sarria L, Bekheit M, Collado F, Almenar-Perez E, Martin-Martinez E, Alegre J, Castro-Marrero J, Fletcher MA, Klimas NG, Oltra E, Nathanson L. Unravelling myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): Gender-specific changes in the microRNA expression profiling in ME/CFS. J Cell Mol Med. 2020 May;24(10):5865-5877. doi: 10.1111/jcmm.15260. Epub 2020 Apr 14.
PubMed 32291908Escorihuela RM, Capdevila L, Castro JR, Zaragoza MC, Maurel S, Alegre J, Castro-Marrero J. Reduced heart rate variability predicts fatigue severity in individuals with chronic fatigue syndrome/myalgic encephalomyelitis. J Transl Med. 2020 Jan 6;18(1):4. doi: 10.1186/s12967-019-02184-z.
PubMed 31906988Bhatia S, Olczyk N, Jason LA, Alegre J, Fuentes-Llanos J, Castro-Marrero J. A Cross-National Comparison of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome at Tertiary Care Settings from the US and Spain. Am J Soc Sci Humanit. 2020;5(1):104-115. doi: 10.20448/801.51.104.115. Epub 2019 Dec 19.
PubMed 34109300Castro-Marrero J, Faro M, Zaragoza MC, Aliste L, de Sevilla TF, Alegre J. Unemployment and work disability in individuals with chronic fatigue syndrome/myalgic encephalomyelitis: a community-based cross-sectional study from Spain. BMC Public Health. 2019 Jun 28;19(1):840. doi: 10.1186/s12889-019-7225-z.
PubMed 31253111Estevez-Lopez F, Castro-Marrero J, Wang X, Bakken IJ, Ivanovs A, Nacul L, Sepulveda N, Strand EB, Pheby D, Alegre J, Scheibenbogen C, Shikova E, Lorusso L, Capelli E, Sekulic S, Lacerda E, Murovska M; European Network on ME/CFS (EUROMENE). Prevalence and incidence of myalgic encephalomyelitis/chronic fatigue syndrome in Europe-the Euro-epiME study from the European network EUROMENE: a protocol for a systematic review. BMJ Open. 2018 Sep 4;8(9):e020817. doi: 10.1136/bmjopen-2017-020817.
PubMed 30181183
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Melatonin Plus Zinc Supplementation on Fatigue, Pain, Sleep Disturbances, Anxiety and Depression, and Autonomic Dysfunction in ME/CFS: a Randomized, Double-blind, Placebo-controlled Study
- ClinicalTrials.gov ID
- NCT05454683
- Acronym / sponsor ID
- MelatoZincME / IC/LV/MEL-ZN/SFC2
- Keywords
- melatonin, zinc, fatigue, sleep quality, quality of life, pain, anxiety and depression, actigraphy
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 106 participants (estimated)
- Lead sponsor
- Laboratorios Viñas, S.A.Industry (pharma, biotech, devices)
- Collaborators
- Laboratorio Echevarne, Hospital Vall d'Hebron
- Study start
- 5 Sep 2022 (estimated)
- Primary completion
- 30 Sep 2024 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 12 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the study is to investigate the effects of oral melatonin and zinc supplementation on core features in individuals with ME/CFS
Detailed description
Myalgic Encephalomyelitis, also known as Chronic Fatigue Syndrome (ME/CFS) is a heterogeneous condition characterized mainly by debilitating and prolonged fatigue, post-exertional malaise (physical, mental and emotional), unrefreshing sleep, cognitive impairment, and orthostatic intolerance with prolonged recovery that is not relieved by rest. Currently, the etiopathogenic mechanisms of ME/CFS are unknown. At present, there is no diagnostic test or effective treatment. MelatoZinc is a food supplement composed of melatonin and zinc, which could contribute to the circadian rhythm homeostasis and regulation of redox imbalance and immune response.
The aim is to evaluate the efficacy and safety of oral treatment with MelatoZinc on the symptomatic complex of fatigue in a larger Spanish ME/CFS population.
This is a single-center, randomized, double-blind, placebo controlled clinical trial. It will include a total of 106 ME/CFS patients who met 2011 ICC criteria for ME/CFS. All patients will take one capsule daily for 16 weeks. Group A will receive MelatoZinc (1 mg melatonin plus 10 mg zinc), and group B will receive a placebo (excipients: isomaltose and magnesium stearate). Clinical symptoms will be evaluated, and standardized questionnaires will be applied to assess the impact of fatigue, pain, anxiety-depression symptoms, sleep quality, dysautonomia, and quality of life. Heart rate variability (HRV) and orthostatic intolerance (10-min NASA Lean Test) will be performed to evaluate autonomic dysfunction. Sleep efficiency will be estimated through an actigraph sensor
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Melatonin plus Zinc | Experimental | Dietary Supplement: melatonin plus zincDietary Supplement: 53 patients treated with melatonin 1 mg plus Zinc 10 mg |
| Placebo | Placebo comparator | Other: isomaltose and magnesium stearate53 patients treated with isomaltose and magnesium stearate (excipients) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients between 18 and 65 years of age.
- Patients with ME/CFS who met the diagnostic criteria (2011 ICC criteria) from the Central Sensitization Syndrome Unit (USSC) at the Vall d'Hebron University Hospital.
- Patients who freely give written consent.
Key exclusion criteria (12 listed)
- Any active medical condition that explained chronic fatigue (untreated hypothyroidism, sleep apnea, narcolepsy, medication side-effects).
- Previous diagnosis not unequivocally resolved (chronic hepatitis, malignancy).
- Past or current psychiatric disorders (major depressive disorder with psychotic or melancholic features, bipolar disorder, schizophrenia, delusional disorder, dementias, anorexia nervosa, bulimia nervosa).
- Participation in another clinical trial of the same or different nature in the 30 days prior to study inclusion.
- In the judgment of the investigator, inability to follow the instructions or to complete the treatment satisfactorily.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| melatonin plus zincAlso: MelatoZincOne capsule with melatonin 1mg plus zinc 10 mg o.d. 30 minutes before bedtime, at least 1 hour after dinner during 4 months | Dietary supplement | Melatonin plus Zinc |
| isomaltose and magnesium stearateAlso: excipientsOne capsule with excipients o.d. 30 minutes before bedtime, at least 1 hour after dinner during 4 months | Other | Placebo |
Primary outcome
Self-reported fatigue as assessed by the 40-item Fatigue Impact Scale (FIS-40) over the baseline in the study participants.
Time frame: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
The FIS-40 includes three subscales of the perceived impact of fatigue: cognitive (10 items), physical (10 items) and psychosocial functions (20 items), each item being scored from 0 (no fatigue) to 4 (severe fatigue). The total score is calculated by adding together the responses from the 40 questions (range 0-160). Higher scores indicate more functional limitations due to fatigue.
14 secondary outcomes
The health-related quality of life (HRQoL) as assessed by the Short-Form 36-Item Health Survey (SF-36) over the baseline in the study participants.
Time frame: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
Sleep disturbances as assessed by the Pittsburgh Sleep Quality Index (PSQI) questionnaire over the baseline in the study participants.
Time frame: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
Sleepiness as assessed by the Epworth Sleepiness Scale (ESS) over the baseline in the study participants.
Time frame: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
Sleep latency as assessed by an actigraph sensor over the baseline in the study participants.
Time frame: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
Sleep onset as assessed by an actigraph sensor over the baseline in the study participants
Time frame: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
Sleep efficiency as assessed by an actigraph sensor over the baseline in the study participants.
Time frame: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
Total sleep time as assessed by an actigraph sensor over the baseline in the study participants.
Time frame: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
Wake time as assessed by an actigraph sensor over the baseline in the study participants.
Time frame: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
Number of awakenings as assessed by an actigraph sensor over the baseline in the study participants.
Time frame: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
Heart rate variability (HRV) as recorded by the FitLab software over the baseline in the study participants.
Time frame: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
Orthostatic intolerance as assessed by the active standing test (10-minute NASA Lean test) over the baseline in the study participants.
Time frame: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
Pain intensity as assessed by a visual analog scale (VAS) over the baseline in the study participants.
Time frame: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
Anxiety and depression symptoms as assessed by the Hospital Anxiety and Depression Scale (HADS) over the baseline in the study participants.
Time frame: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
Side effect of treatment
Time frame: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2022.
- Background: PubMed 34201806Castro-Marrero J, Zaragoza MC, Lopez-Vilchez I, Galmes JL, Cordobilla B, Maurel S, Domingo JC, Alegre-Martin J. Effect of Melatonin Plus Zinc Supplementation on Fatigue Perception in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial. Antioxidants (Basel). 2021 Jun 23;10(7):1010. doi: 10.3390/antiox10071010.
- Background: PubMed 35229657Castro-Marrero J, Domingo JC, Cordobilla B, Ferrer R, Giralt M, Sanmartin-Sentanes R, Alegre-Martin J. Does Coenzyme Q10 Plus Selenium Supplementation Ameliorate Clinical Outcomes by Modulating Oxidative Stress and Inflammation in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome? Antioxid Redox Signal. 2022 Apr;36(10-12):729-739. doi: 10.1089/ars.2022.0018.
- Background: PubMed 34575280Castro-Marrero J, Zacares M, Almenar-Perez E, Alegre-Martin J, Oltra E. Complement Component C1q as a Potential Diagnostic Tool for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Subtyping. J Clin Med. 2021 Sep 15;10(18):4171. doi: 10.3390/jcm10184171.
- Background: PubMed 34444817Castro-Marrero J, Segundo MJ, Lacasa M, Martinez-Martinez A, Sentanes RS, Alegre-Martin J. Effect of Dietary Coenzyme Q10 Plus NADH Supplementation on Fatigue Perception and Health-Related Quality of Life in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients. 2021 Jul 30;13(8):2658. doi: 10.3390/nu13082658.
- Background: PubMed 34300271Baklund IH, Dammen T, Moum TA, Kristiansen W, Duarte DS, Castro-Marrero J, Helland IB, Strand EB. Evaluating Routine Blood Tests According to Clinical Symptoms and Diagnostic Criteria in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. J Clin Med. 2021 Jul 14;10(14):3105. doi: 10.3390/jcm10143105.
- Background: PubMed 34071326Capdevila L, Castro-Marrero J, Alegre J, Ramos-Castro J, Escorihuela RM. Analysis of Gender Differences in HRV of Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Using Mobile-Health Technology. Sensors (Basel). 2021 May 28;21(11):3746. doi: 10.3390/s21113746.
- Background: PubMed 33353469Domingo JC, Cordobilla B, Ferrer R, Giralt M, Alegre-Martin J, Castro-Marrero J. Are Circulating Fibroblast Growth Factor 21 and N-Terminal Prohormone of Brain Natriuretic Peptide Promising Novel Biomarkers in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome? Antioxid Redox Signal. 2021 Jun 20;34(18):1420-1427. doi: 10.1089/ars.2020.8230. Epub 2021 Feb 11.
- Background: PubMed 33329554Gomez-Mora E, Carrillo J, Urrea V, Rigau J, Alegre J, Cabrera C, Oltra E, Castro-Marrero J, Blanco J. Impact of Long-Term Cryopreservation on Blood Immune Cell Markers in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Implications for Biomarker Discovery. Front Immunol. 2020 Nov 17;11:582330. doi: 10.3389/fimmu.2020.582330. eCollection 2020.
- Background: PubMed 33046133Giloteaux L, O'Neal A, Castro-Marrero J, Levine SM, Hanson MR. Cytokine profiling of extracellular vesicles isolated from plasma in myalgic encephalomyelitis/chronic fatigue syndrome: a pilot study. J Transl Med. 2020 Oct 12;18(1):387. doi: 10.1186/s12967-020-02560-0.
- Background: PubMed 32455633Estevez-Lopez F, Mudie K, Wang-Steverding X, Bakken IJ, Ivanovs A, Castro-Marrero J, Nacul L, Alegre J, Zalewski P, Slomko J, Strand EB, Pheby D, Shikova E, Lorusso L, Capelli E, Sekulic S, Scheibenbogen C, Sepulveda N, Murovska M, Lacerda E. Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology. J Clin Med. 2020 May 21;9(5):1557. doi: 10.3390/jcm9051557.
- Background: PubMed 32291908Cheema AK, Sarria L, Bekheit M, Collado F, Almenar-Perez E, Martin-Martinez E, Alegre J, Castro-Marrero J, Fletcher MA, Klimas NG, Oltra E, Nathanson L. Unravelling myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): Gender-specific changes in the microRNA expression profiling in ME/CFS. J Cell Mol Med. 2020 May;24(10):5865-5877. doi: 10.1111/jcmm.15260. Epub 2020 Apr 14.
- Background: PubMed 31906988Escorihuela RM, Capdevila L, Castro JR, Zaragoza MC, Maurel S, Alegre J, Castro-Marrero J. Reduced heart rate variability predicts fatigue severity in individuals with chronic fatigue syndrome/myalgic encephalomyelitis. J Transl Med. 2020 Jan 6;18(1):4. doi: 10.1186/s12967-019-02184-z.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
José Alegre, MD, PhD principal investigator
Vall d'Hebron University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing melatonin plus zinc and isomaltose and magnesium stearate in people with Chronic Fatigue Syndrome and Myalgic Encephalomyelitis, run by Laboratorios Viñas, S.A. at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact José Alegre, MD, PhD (+34934893000 ext. 3753, jalegre@vhebron.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Self-reported fatigue as assessed by the 40-item Fatigue Impact Scale (FIS-40) over the baseline in the study participants. (time frame: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05454683, which also lists 27 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2022.