Clinical trial NCT05454683: Melatonin and Zinc Administration on Cardinal Symptoms in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
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
Lead sponsor: Laboratorios Viñas, S.A.
Sponsor class: INDUSTRY
Collaborators: name: Laboratorio Echevarne
name: Hospital Vall d'Hebron
First posted: 2022-07-12
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Eligibility criteria: Inclusion Criteria:

1. Patients between 18 and 65 years of age.
2. 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.
3. Patients who freely give written consent.

Exclusion Criteria:

1. Any active medical condition that explained chronic fatigue (untreated hypothyroidism, sleep apnea, narcolepsy, medication side-effects).
2. Previous diagnosis not unequivocally resolved (chronic hepatitis, malignancy).
3. Past or current psychiatric disorders (major depressive disorder with psychotic or melancholic features, bipolar disorder, schizophrenia, delusional disorder, dementias, anorexia nervosa, bulimia nervosa).
4. Participation in another clinical trial of the same or different nature in the 30 days prior to study inclusion.
5. In the judgment of the investigator, inability to follow the instructions or to complete the treatment satisfactorily.
6. Failure to provide signed informed consent.
7. Current consumption of medications that may interfere with the results and/or whose withdrawal may be a relevant problem.
8. Anticoagulant treatment.
9. Pregnancy or breast-feeding, or had not used oral contraceptives or other hormonal preparations in the previous 6 months.
10. Smoking, alcohol intake or substance abuse.
11. Severe obesity (class 3 BMI ≥ 40 kg/m2).
12. Hypersensitivity to melatonin and/or zinc dietary supplements.

Primary outcomes:
measure: Self-reported fatigue as assessed by the 40-item Fatigue Impact Scale (FIS-40) over the baseline in the study participants.
timeFrame: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
Secondary outcomes:
measure: 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.
timeFrame: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
measure: Sleep disturbances as assessed by the Pittsburgh Sleep Quality Index (PSQI) questionnaire over the baseline in the study participants.
timeFrame: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
measure: Sleepiness as assessed by the Epworth Sleepiness Scale (ESS) over the baseline in the study participants.
timeFrame: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
measure: Sleep latency as assessed by an actigraph sensor over the baseline in the study participants.
timeFrame: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
measure: Sleep onset as assessed by an actigraph sensor over the baseline in the study participants
timeFrame: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
measure: Sleep efficiency as assessed by an actigraph sensor over the baseline in the study participants.
timeFrame: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
measure: Total sleep time as assessed by an actigraph sensor over the baseline in the study participants.
timeFrame: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
measure: Wake time as assessed by an actigraph sensor over the baseline in the study participants.
timeFrame: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
measure: Number of awakenings as assessed by an actigraph sensor over the baseline in the study participants.
timeFrame: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
measure: Heart rate variability (HRV) as recorded by the FitLab software over the baseline in the study participants.
timeFrame: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
measure: Orthostatic intolerance as assessed by the active standing test (10-minute NASA Lean test) over the baseline in the study participants.
timeFrame: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
measure: Pain intensity as assessed by a visual analog scale (VAS) over the baseline in the study participants.
timeFrame: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
measure: Anxiety and depression symptoms as assessed by the Hospital Anxiety and Depression Scale (HADS) over the baseline in the study participants.
timeFrame: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
measure: Side effect of treatment
timeFrame: During 4 months of treatment and 8 weeks after discontinuation of dietary therapy
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Vall d'Hebron University Hospital
Study officials:
affiliation: Vall d'Hebron University Hospital
name: José Alegre, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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