Clinical trial NCT03036293: Tenoten® in the Treatment of Somatoform, Stress-related and Other Neurotic Disorders
Official title: International Multicenter, Double-blind, Randomized Placebo-controlled Phase IV Clinical Trial of Different Dosing Regimens of Tenoten® in the Treatment of Anxiety in Patients With Somatoform, Stress-related and Other Neurotic Disorders
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Anxiety
Lead sponsor: Materia Medica Holding
Sponsor class: INDUSTRY
First posted: 2017-01-30
Enrollment: 390
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purposes of this study are:

* To further examine the efficacy and safety of Tenoten® in the treatment of anxiety in patients with somatoform, stress-related and other neurotic disorders.
* To compare the efficacy of two dosing regimens of Tenoten® (4 tablets daily vs.8 tablets daily, both for 12 weeks) in the treatment of anxiety in patients with somatoform, stress-related and other neurotic disorders.

Detailed description: Design: an international, a multicenter, double-blind, randomized, parallel group placebo-controlled trial to evaluate efficacy and safety of study treatment.

The study will enroll outpatient subjects of both genders aged 18-45 years with verified diagnoses of somatoform, stress-related and other neurotic disorders (F43, F45, F48) and signs of clinically relevant anxiety according to The Hospital Anxiety and Depression scale (HADS).

After signing the informed consent form to participate in the clinical study the subject will be interviewed (complaints, medical history, concomitant therapy) and objective examination will be performed; the subject will fill HADS scale. The severity of anxiety at screening should be ≥ 11 according to HADS. If the subject meets inclusion criteria and has no exclusion criteria he/she will be enrolled into the study. The investigator will determine the severity of anxiety using НАМ-А scale; the subject will fill EQ-5D-3L questionnaire. At Visit 1 (Day 1) the subject will be randomized into one of the treatment groups:

* Group 1: Tenoten® at 2 tablets twice daily (4 tablets/day);
* Group 2: Placebo at 2 tablets twice daily (4 tablets/day);
* Group 3: Tenoten® at 2 tablets 4 daily (8 tablets/day).
* Group 4: Placebo at 2 tablets 4 daily (8 tablets/day). The first dose should be administered at Visit 1 after the visit procedures are completed. Further administration of the study product will be made according to the dosing scheme. The subject will administer the study product and will be followed for 12 weeks during which additional three visits will be made. At Visit 2 (Week 4), Visit 3 (Week 8) and Visit 4 (Week 12) the physician will record patients' complaints and physical examination data, fill HAM-A scale, check the study and concomitant therapy, assess treatment safety and patient compliance with the study treatment. At the final Visit 4 the subject will fill EQ-5D-3L questionnaire and the investigator will fill the Clinical Global Impression Scale Efficacy Index (CGI-EI).

Subjects will be allowed to take symptomatic therapy and medications for their co-morbidities during the study, except for the medicines listed in "Prohibited therapy".

Eligibility criteria: Inclusion Criteria:

1. Patients of both sexes aged 18-45 years (inclusive).
2. Patients diagnosed with somatoform, stress-related, and other neurotic disorders (F43, F45, and F48), in accordance with the ICD-10 criteria.
3. A moderate and severe anxiety (HADS score ≥ 11) documented at screening.
4. Patients providing signed Informed Consent form for participation in the clinical trial.
5. Patients of reproductive age (of both sexes) using contraceptives and contraceptive methods during the study and for 30 days after the end of participation in the trial.

Exclusion Criteria:

1. Moderate and severe depression symptoms recorded at screening (HADS score ≥ 11).
2. Organic, including symptomatic, mental disorders (F00-09).
3. Mental and behavioural disorders due to psychoactive substance use (F10-19).
4. Schizophrenia, schizotypal and delusional disorders (F20-29).
5. Mood \[affective\] disorders(F30-39).
6. Phobic (F40) and other anxiety disorders (F41), obsessive-compulsive disorder (F42), dissociative \[conversion\] disorders (F44), depersonalization-derealization syndrome (F48.1).
7. Behavioral syndromes associated with physiological disturbances and physical factors (F50-59).
8. Disorders of adult personality and behavior (F60-69).
9. Intellectual disabilities (F70-79).
10. Inflammatory and traumatic brain injuries with permanent neurological deficit.
11. Prior diagnosis of a class III or IV cardiovascular disease (according to the New York Heart Association, 1964)
12. Malignant neoplasms/suspected malignant neoplasms.
13. An allergy/intolerance to any of the components of medications used in the treatment.
14. Malabsorption syndrome (including hereditary or acquired lactase or other disaccharidase deficiency) and galactosemia.
15. Any conditions that, from investigator's point of view, may affect the patient's ability to participate in the trial.
16. Hospitalizations or surgeries scheduled for any date during the participation in the study.
17. Patients who, from investigator's point of view, will fail to comply with the observation requirements of the trial or with the dosing regimen of the study drugs.
18. Use of drugs listed in "Prohibited therapy" within a month prior to enrollment.
19. Drug addiction, alcohol use in the amount over 2 units of alcohol a day.
20. Pregnant or breast-feeding women.
21. Participation in other clinical trials within 3 month prior to the enrollment in this study.
22. Patients are related to the research personnel of the investigative site who are directly involved in the trial, or patients who are the immediate family member of the researcher. The 'immediate family member' includes husband/wife, parents, children or brothers (or sisters), regardless of whether they are natural or adopted.
23. Patients working for OOO "NPF "MATERIA MEDICA HOLDING", i.e. the company's employee, temporary contract worker, or appointed official responsible for carrying out the research (or the immediate relative).

Primary outcomes:
measure: Change From Baseline in the Mean HAM-A Score at 12 Weeks of Treatment: 1. Group 1 (Tenoten®, 4 Tablets a Day); 2. Group 3 (Tenoten®, 8 Tablets a Day).
timeFrame: 12 weeks
Secondary outcomes:
measure: Change From Baseline in the Mean HAM-A Score at 4 Weeks of Treatment: 1.1. Group 1 (Tenoten®, 4 Tablets a Day); 1.2. Group 3 (Tenoten®, 8 Tablets a Day).
timeFrame: 4 weeks
measure: The Mean HAM-A Score at 8 Weeks of Treatment: 2.1. Group 1 (Tenoten®, 4 Tablets a Day); 2.2. Group 3 (Tenoten®, 8 Tablets a Day).
timeFrame: 8 weeks
measure: Percentage of Patients Had at Least a 50% Improvement in the HAM-A Score: 3.1. Group 1 (Tenoten® 4 Tablets a Day): After 4, 8 and 12 Weeks; 3.2. Group 3 (Tenoten® 8 Tablets a Day): After 4, 8 and 12 Weeks.
timeFrame: 4,8,12 weeks
measure: Percentage of Patients With no Anxiety (HAM-A Score <14) in: 4.1. Group 1 (Tenoten®, 4 Tablets a Day); After 4, 8 and 12 Weeks; 4.3. Group 3 (Tenoten®, 4 Tablets a Day); After 4, 8 and 12 Weeks.
timeFrame: 4,8,12 weeks
measure: Change From Baseline in the Total EQ-5D-3L Score at 12 Weeks of Treatment in Patients From: 5.1. Group 1 (Tenoten®, 4 Tablets a Day); 5.2. Group 3 (Tenoten®, 8 Tablets a Day).
timeFrame: 12 weeks
measure: Total CGI Scores in Patients From: 6.1. Group 1 (Tenoten®, 4 Tablets a Day); 6.2. Group 3 (Tenoten®, 8 Tablets a Day).
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Almaty
country: Kazakhstan
facility: Kazakh National Medical University named after S.D. Asfendiyarov
city: Shymkent
country: Kazakhstan
facility: South - Kazakhstan State Pharmaceutical Academy
city: Chelyabinsk
country: Russian Federation
facility: Municipal Autonomous Healthcare Institution Order of the Red Banner of Labor City Clinical Hospital No. 1
city: Kazan'
country: Russian Federation
facility: Federal State Budgetary Educational Institution of Higher Education "Kazan Medical University" of the Ministry of Healthcare of the Russian Federation
city: Kazan'
country: Russian Federation
facility: The State Autonomic Health Care institution "Interregional clinical and diagnostical center"
city: Kazan'
country: Russian Federation
facility: LLC "City Center for Neurology and Pain Management"
city: Korolev
country: Russian Federation
facility: Limited Liability Company "Family policlinic no. 4"
city: Moscow
country: Russian Federation
facility: State Budget Health Care institution of Moscow the City "Scientific and practical psychoneurological center n.a. Z.P. Solovyov" of the Administration of Health Care of Moscow City
city: Moscow
country: Russian Federation
facility: The State Budget Health Care institution of Moscow the City "City clinical hospital No. 12 of the Administration of Health Care of Moscow City"
city: Moscow
country: Russian Federation
facility: Pirogov Russian National Research Medical University
city: Moscow
country: Russian Federation
facility: The State Budget Educational institution of High Professional Training I.M. Sechenov First Moscow State Medical University of Ministry of Health Care of the Russian Federation, Hospital of nervous diseases A.Y. Kozhevnikov
city: Nizhny Novgorod
country: Russian Federation
facility: State budgetary institution of public health services of the Nizhniy Novgorod region "Nizhegorod Regional Clinical Hospital named after NA Semashko"
city: Novosibirsk
country: Russian Federation
facility: LLC "City Neurological Center" Sibneyromed "
city: Saint Petersburg
country: Russian Federation
facility: Pavlov First Saint Petersburg State Medical University/Department of Neurology and Manual Medicine
city: Saint Petersburg
country: Russian Federation
facility: Pavlov First Saint Petersburg State Medical University/Department of Neurology with Clinic
city: Samara
country: Russian Federation
facility: State-Funded Healthcare Institution of the Samara Region "Samara City N.I. Pirogov Clinical Hospital №1"
city: Saratov
country: Russian Federation
facility: Saratov State Medical University named after V. I. Razumovsky
city: Smolensk
country: Russian Federation
facility: The State Budget Educational institution of High Professional Training Smolensk State Medical University of Ministry of Health Care of the Russian Federation, Smolensk regional clinical hospital
city: Vladimir
country: Russian Federation
facility: The state budgetary health care institution of the Vladimir region "Regional Clinical Hospital"
city: Volgograd
country: Russian Federation
facility: Volgograd State Medical University
city: Yaroslavl'
country: Russian Federation
facility: The State Health Care Institution Yaroslavl region "Clinical Hospital №8
city: Yaroslavl
country: Russian Federation
facility: State Institution of Health of the Yaroslavl Region Clinical Hospital No. 8
Study officials:
affiliation: I.M. Sechenov First Moscow State Medical University (Sechenov University)
name: Vladimir Parfenov, DrMedSci
role: PRINCIPAL_INVESTIGATOR
References:
citation: Parfenov VA, Kamchatnov PR, Khasanova DR, Bogdanov EI, Lokshtanova TM, Amelin AV, Maslova NN, Pizova NV, Belskaya GN, Barantsevich ER, Duchshanova GA, Kamenova SU, Kolokolov OV, Glazunov AB. The randomized clinical trial results of the anxiety treatment in patients with somatoform dysfunction and neurotic disorders. Sci Rep. 2021 Dec 20;11(1):24282. doi: 10.1038/s41598-021-03727-5.