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

July 7, 2022 updated by: Laboratorios Viñas, S.A.

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

106

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Spain
      • Barcelona, Spain, 08035
        • Recruiting
        • Vall d'Hebron University Hospital
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Melatonin plus Zinc

Dietary Supplement:

53 patients treated with melatonin 1 mg plus Zinc 10 mg
Dietary supplement: melatonin plus zinc
One capsule with melatonin 1mg plus zinc 10 mg o.d. 30 minutes before bedtime, at least 1 hour after dinner during 4 months
Other Names:
  • MelatoZinc
PLACEBO_COMPARATOR: Placebo
53 patients treated with isomaltose and magnesium stearate (excipients)
Other: isomaltose and magnesium stearate
One capsule with excipients o.d. 30 minutes before bedtime, at least 1 hour after dinner during 4 months
Other Names:
  • excipients

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
During 4 months of treatment and 8 weeks after discontinuation of dietary therapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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.
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
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.
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
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).
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
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.
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
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.
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
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.
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
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.
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
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.
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
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.
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
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.
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
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.
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
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).
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
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).
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
Treatment side effects will be collected from each participant during clinical trial.
During 4 months of treatment and 8 weeks after discontinuation of dietary therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Laboratorios Viñas, S.A.

Collaborators

Hospital Vall d'Hebron
Laboratorio Echevarne

Investigators

  • Principal Investigator: José Alegre, MD, PhD, Vall d'Hebron University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

September 5, 2022

Primary Completion (ANTICIPATED)

September 30, 2024

Study Completion (ANTICIPATED)

December 31, 2024

Study Registration Dates

First Submitted

June 30, 2022

First Submitted That Met QC Criteria

July 7, 2022

First Posted (ACTUAL)

July 12, 2022

Study Record Updates

Last Update Posted (ACTUAL)

July 12, 2022

Last Update Submitted That Met QC Criteria

July 7, 2022

Last Verified

July 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IC/LV/MEL-ZN/SFC2

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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