Melatonin and Zinc Administration on Cardinal Symptoms in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

NCT05454683 | Unknown

• 1 other identifier: IC/LV/MEL-ZN/SFC2
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Chronic Fatigue Syndrome; Myalgic Encephalomyelitis

Keywords

melatonin; zinc; fatigue; sleep quality; quality of life; pain; anxiety and depression; actigraphy; heart rate variability; orthostatic intolerance

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  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.

  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.

  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.

  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

  During 4 months of treatment and 8 weeks after discontinuation of dietary therapy

Study Arms (2)

Melatonin plus Zinc

EXPERIMENTAL

Dietary Supplement: 53 patients treated with melatonin 1 mg plus Zinc 10 mg

Dietary Supplement: melatonin plus zinc

Placebo

PLACEBO COMPARATOR

53 patients treated with isomaltose and magnesium stearate (excipients)

Other: isomaltose and magnesium stearate

Interventions

melatonin plus zinc DIETARY_SUPPLEMENT

One capsule with melatonin 1mg plus zinc 10 mg o.d. 30 minutes before bedtime, at least 1 hour after dinner during 4 months

Also known as: MelatoZinc

Melatonin plus Zinc

isomaltose and magnesium stearate OTHER

One capsule with excipients o.d. 30 minutes before bedtime, at least 1 hour after dinner during 4 months

Also known as: excipients

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• In the judgment of the investigator, inability to follow the instructions or to complete the treatment satisfactorily.
• Failure to provide signed informed consent.
• 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.

Sponsors & Collaborators

• Laboratorios Viñas, S.A.: lead
• Laboratorio Echevarne: collaborator
• Hospital Vall d'Hebron: collaborator

Study Sites (1)

Vall d'Hebron University Hospital

Barcelona, 08035, Spain

RECRUITING

Related Publications (27)

• 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.

  PMID: 34201806 BACKGROUND

• Castro-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.

  PMID: 35229657 BACKGROUND

• Castro-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.

  PMID: 34575280 BACKGROUND

• Castro-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.

  PMID: 34444817 BACKGROUND

• Baklund 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.

  PMID: 34300271 BACKGROUND

• Capdevila 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.

  PMID: 34071326 BACKGROUND

• Domingo 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.

  PMID: 33353469 BACKGROUND

• Gomez-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.

  PMID: 33329554 BACKGROUND

• Giloteaux 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.

  PMID: 33046133 BACKGROUND

• Estevez-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.

  PMID: 32455633 BACKGROUND

• Cheema 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.

  PMID: 32291908 BACKGROUND

• Escorihuela 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.

  PMID: 31906988 BACKGROUND

• Bhatia 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.

  PMID: 34109300 BACKGROUND

• Castro-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.

  PMID: 31253111 BACKGROUND

• Estevez-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.

  PMID: 30181183 BACKGROUND

• Cambras T, Castro-Marrero J, Zaragoza MC, Diez-Noguera A, Alegre J. Circadian rhythm abnormalities and autonomic dysfunction in patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. PLoS One. 2018 Jun 6;13(6):e0198106. doi: 10.1371/journal.pone.0198106. eCollection 2018.

  PMID: 29874259 BACKGROUND

• Castro-Marrero J, Zaragoza MC, Gonzalez-Garcia S, Aliste L, Saez-Francas N, Romero O, Ferre A, Fernandez de Sevilla T, Alegre J. Poor self-reported sleep quality and health-related quality of life in patients with chronic fatigue syndrome/myalgic encephalomyelitis. J Sleep Res. 2018 Dec;27(6):e12703. doi: 10.1111/jsr.12703. Epub 2018 May 16.

  PMID: 29770505 BACKGROUND

• Castro-Marrero J, Serrano-Pertierra E, Oliveira-Rodriguez M, Zaragoza MC, Martinez-Martinez A, Blanco-Lopez MDC, Alegre J. Circulating extracellular vesicles as potential biomarkers in chronic fatigue syndrome/myalgic encephalomyelitis: an exploratory pilot study. J Extracell Vesicles. 2018 Mar 22;7(1):1453730. doi: 10.1080/20013078.2018.1453730. eCollection 2018.

  PMID: 29696075 BACKGROUND

• Sotzny F, Blanco J, Capelli E, Castro-Marrero J, Steiner S, Murovska M, Scheibenbogen C; European Network on ME/CFS (EUROMENE). Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Evidence for an autoimmune disease. Autoimmun Rev. 2018 Jun;17(6):601-609. doi: 10.1016/j.autrev.2018.01.009. Epub 2018 Apr 7.

  PMID: 29635081 BACKGROUND

• Scheibenbogen C, Freitag H, Blanco J, Capelli E, Lacerda E, Authier J, Meeus M, Castro Marrero J, Nora-Krukle Z, Oltra E, Strand EB, Shikova E, Sekulic S, Murovska M. The European ME/CFS Biomarker Landscape project: an initiative of the European network EUROMENE. J Transl Med. 2017 Jul 26;15(1):162. doi: 10.1186/s12967-017-1263-z.

  PMID: 28747192 BACKGROUND

• Castro-Marrero J, Faro M, Aliste L, Saez-Francas N, Calvo N, Martinez-Martinez A, de Sevilla TF, Alegre J. Comorbidity in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Nationwide Population-Based Cohort Study. Psychosomatics. 2017 Sep-Oct;58(5):533-543. doi: 10.1016/j.psym.2017.04.010. Epub 2017 Apr 21.

  PMID: 28596045 BACKGROUND

• 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.

  PMID: 28052319 BACKGROUND

• 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.

  PMID: 26212172 BACKGROUND

• Faro M, Saez-Francas N, Castro-Marrero J, Aliste L, Fernandez de Sevilla T, Alegre J. Gender differences in chronic fatigue syndrome. Reumatol Clin. 2016 Mar-Apr;12(2):72-7. doi: 10.1016/j.reuma.2015.05.007. Epub 2015 Jul 17. English, Spanish.

  PMID: 26190206 BACKGROUND

• 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.

  PMID: 25386668 BACKGROUND

• 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.

  PMID: 23600892 BACKGROUND

• 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.

  PMID: 23514202 BACKGROUND

MeSH Terms

Conditions

Fatigue Syndrome, Chronic; Fatigue; Sleep Initiation and Maintenance Disorders; Pain; Anxiety Disorders; Depression; Orthostatic Intolerance

Interventions

Melatonin; Zinc; Isomaltose; stearic acid; Excipients

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Encephalomyelitis; Neuroinflammatory Diseases; Nervous System Diseases; Neuromuscular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Mental Disorders; Neurologic Manifestations; Behavioral Symptoms; Behavior; Primary Dysautonomias; Autonomic Nervous System Diseases

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals; Glucans; Polysaccharides; Carbohydrates; Disaccharides; Oligosaccharides; Sugars; Pharmaceutical Vehicles; Pharmaceutic Aids; Pharmaceutical Preparations; Specialty Uses of Chemicals; Chemical Actions and Uses

Study Officials

• José Alegre, MD, PhD

  Vall d'Hebron University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

José Alegre, MD, PhD

CONTACT

+34934893000; jalegre@vhebron.net

Jesús Castro, PhD

CONTACT

+34934893000; jesus.castro@vhir.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2022
• First Posted: July 12, 2022
• Study Start: September 5, 2022
• Primary Completion: September 30, 2024
• Study Completion: December 31, 2024
• Last Updated: July 12, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)