A pilot clinical trial with human alpha-1 antitrypsin in patients with chronic fatigue syndrome

Phase 1

• Conditions: Patients with chronic fatigue syndrome; MedDRA version: 18.0Level: PTClassification code 10008874Term: Chronic fatigue syndromeSystem Organ Class: 10018065 - General disorders and administration site conditions; MedDRA version: 18.0Level: SOCClassification code 10018065Term: General disorders and administration site conditionsSystem Organ Class: 10018065 - General disorders and administration site conditions; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2014-002007-13-ES
• Lead Sponsor: Instituto Grifols, S.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-07-15
• Last Update Posted: 22 January 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 26

Inclusion Criteria

1.Male or female aged 18 to 65 years.
2.Subjects with a BMI ? 30 Kg/m2.
3.Subjects who meet ?Myalgic Encephalomyelitis: International Consensus Criteria, 2011? and with a diagnostics of CFS for more than 12 months.
4.Subjects who understand and voluntarily signed by written his/her clinical trial participation consent.
5.Subjects who judged to be reliable and demonstrated a degree of understanding that allowed them to communicate intelligibly, according to the investigator?s criteria, so it can be successfully applied the monitoring clinical instruments of CFS proposed in the clinical trial.
6.Subjects must be willing to comply with all aspects of the clinical trial protocol, including blood sampling and limitation in medication to alleviate CFS-symptoms.
7.Subjects who have successfully completed the Screening Period.
8.Subjects with elastase activity in PBMC exceeding 150 units/mg prior to start Run-in Period (Week -6).
9.Subjects who have successfully completed the Run-in Period.
10.Subjects with elastase activity in PBMC exceeding 150 units/mg at the Baseline Visit 1 (Week 0).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6

Exclusion Criteria

1.Subjects with any severe congenital deficiency of AAT.
2.Subjects who are active smokers within 6 months prior to Enrollment Visit.
3.Subjects currently receiving, or having received within 3 months prior to the Enrollment Visit treatment with human AAT.
4.Subjects with a history of intolerance to any component or excipient of the investigational products (AAT, chloride, phosphate, sodium).
5.Subjects with a history of anaphylactic reactions or severe reactions to any blood-derived product.
6.Subjects with a history of chronic alcoholism or illicit drug abuse (addiction) in the preceding 12 months prior to the Enrollment Visit.
7.Subjects with a known selective IgA deficiency and serum antibodies anti-IgA.
8.Subjects with any medical condition in the moment of the Enrollment Visit determined by laboratory tests, which is likely to significantly interfere in the clinical manifestation of CFS. Here are detailed some of these medical conditions:
?Serum AST, ALT, ALP or total bilirubin levels exceeding more than 1.5 times the upper limit of normal (ULN) for the expected normal range for the testing laboratory.
?Serum creatinine or urea levels exceeding more than 1.5 time the ULN for the expected normal range for the testing laboratory.
?Serum CK totals levels exceeding the ULN for the expected normal range for the testing laboratory.
?Serum TSH levels exceeding the ULN for the expected normal range for the testing laboratory.
?Serum title of ANA exceeding 1:160 dilutions.
?Positive serum FR as per positivity criteria established for the testing laboratory.
9.Subjects suffering from a disease or medical condition that could increase associated risks to subjects? participation in the clinical trial, or interfere with the interpretation of the study results, and according to the investigator?s criteria, it would be inappropriate for the subjects? participation in the clinical trial. These diseases include, but are not limited to major depressive disorders with psychotic or melancholic features as bipolar disorders, schizophrenia, dementia, anorexia or nervous bulimia.
10.Subjects currently receiving, or have received within 3 months prior to the Enrollment Visit, any investigational medicinal product or device.
11.Females who are pregnant, breastfeeding, of child-bearing potential, or unwilling to practice a highly effective method of contraception (oral, injectable or implanted hormonal methods of contraception, placement of an intrauterine device or intrauterine system, condom or occlusive cap with spermicidal foam/gel/film/cream/suppository, male sterilization, or true abstinence*) throughout the study.
* True abstinence: When this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods], declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception.)
12.Subjects pending for a resolution of a dispute or compensatory process, caused by their medical condition.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the potential clinical effect of weekly intravenous infusions of human alpha-1 antitrypsin (AAT) in subjects suffering from CFS by means of the change in elastase activity in peripheral blood mononuclear cells (PBMC).;Secondary Objective: Safety of AAT therapy in subjects with CFS and without congenital deficiency of AAT will also be assessed.;Primary end point(s): Change in elastase activity in PBMC.;Timepoint(s) of evaluation of this end point: 12 weeks treatment

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): ?Change in tiredness score evaluated by Fatigue Severity Scale (FSS).<br>?Change in health-related quality of life measured by the Medical Outcomes Study-36 Item Short Form Health Survey (SF-36).;Timepoint(s) of evaluation of this end point: 12 weeks treatment