TEsting METformin Against Cognitive Decline in HD
- Registration Number
- NCT04826692
- Lead Sponsor
- Instituto de Investigacion Sanitaria La Fe
- Brief Summary
Multicenter, randomized, double-blind, placebo-controlled, parallel group study to assess the efficacy and safety of metformin treatment at a dose of 1700 mg / day in adults with Huntington's disease.
The study consists of a screening period (2 to 4 weeks), followed by a 52-week double-blind treatment period and a follow-up visit (one month after the end of treatment).
- Detailed Description
Multicenter, randomized, double-blind, placebo-controlled, parallel group study to assess the efficacy and safety of treatment with metformin at a dose of 1700 mg / day in adults with HD.
A total recruitment of 60 patients is expected, which will be randomized in a 1: 1 ratio. 30 patients will receive metformin 1700 g / day, or placebo, for 52 weeks.
Patients will begin taking low doses of metformin, to facilitate tolerance and decrease intestinal discomfort. Half the daily dose (425 mg twice daily) will be administered over four weeks, along with the main meals. Patients who tolerate this dose well will continue with treatment by taking 850mg twice daily. Patients who don´t tolerate the initial dose (425 mg twice daily) will be withdrawn from the study.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 60
- Symptomatic positive clinical diagnosis of Huntington disease.
- Presence of 36 CAG repeats (or more) in the hunting gene based on centralized CAG analysis.
- Men or women between 21-65 years of age, inclusive, with an onset of HD at 18 years of age or older.
- Women of childbearing potential (women who are not postmenopausal children or who have not undergone surgical sterilization at times) will need to be using a contraceptive method for 30 days before beginning study treatment, and will have contact with at least two methods of birth control throughout the duration of the study and up to 30 days after taking the last dose of treatment.
- A sum of > 4 points on the UHDRS-TMS scale and a diagnostic confidence level of 4.
- Scale of independence ≥ 75%.
- Score on the UHDRS-TFC scale ≥ 8 at the screening visit.
- They must be trained and willing to provide written informed consent prior to any procedure related to the study to be performed at the screening visit. Patients with a legal guardian must be determined according to local requirements.
- They must be trained and will require taking oral medication and will need to be determined to comply with the specific study procedures.
- They must be able to travel to the study center and, in the judgment of the investigator, demonstrate that it is probable that they can continue traveling during the study.
- Availability and willingness of a caregiver, informant, or family member to provide information during study visits that evaluate PBA-s. It is recommended that the caregiver be someone who cares for the patient at least 2 to 3 times a week and at least 3 hours per occasion. The suitability of the caregiver must be judged by the investigator.
- The participant has taken metformin in the last three months before the start of the study.
- The participant has diabetes of any kind.
- The participant is pregnant or lactating.
- The participant has a medical condition other than HD (metabolism, kidney function, liver function, heart problems, etc.), or any contraindication against metformin.
- The participant has an uncontrolled psychiatric condition.
- Participant is allergic to metformin or any of the other ingredients of this medicine.
- The participant has kidney problems [creatinine clearance <60 ml / min calculated using Cockcroft-Gault formula] or liver problems.
- The participant is dehydrated, from prolonged or severe diarrhea, or has vomited several times.
- The participant has a serious infection.
- The participant has been treated for heart failure or has recently had a heart attack, has severe circulation problems, or is having difficulty breathing.
- The participant drinks> 6 units / day of alcohol (alcoholism).
- Participants diagnosed with oncological disease.
- Participants with a suicidal propensity, with an affirmative answer in items 4 or 5 in the C-SSRS at the screening visit.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Metformin Metformin Therapeutic group: Biguanidines (antidiabetic) Administration way: Oral Initial dose: 425 mg twice daily Maximum dose: 850 mg, twice daily Treatment duration: 12 months Placebo Placebo Therapeutic group: NA Administration way: Oral Initial dose: 425 mg twice daily Maximum dose: 850 mg, twice daily Treatment duration: 12 months
- Primary Outcome Measures
Name Time Method Evaluate the effect of metformin on the scores obtained in different cognitive subtests that make up the Unified Huntington's Disease Rating Scale (UHDRS). Baseline - Week 52 The tests that make up this subscale are words and interference in the Stroop test.
The Stroop test was performed to determine selective attention and inhibitory response (selective response to stimuli) to recognize a different stimulus among others. The test involves three kinds of stimuli: three columns of color names printed in black (condition A), three columns with different colors (red, green, blue or black) (condition B), and three columns of color names printed in a color that does not necessarily correspond to the word (for For example, the word "green" printed in blue, (condition C). The 3 parts of the test consist of A. speed of reading the words (names of colors printed in black), B. speed of nomination, the subject must name the colors. C. inhibitory response, called the interference test, where the subject must name the color in which the word with the name of the other color.
The test has 45 seconds time limit.Evaluate the effect of metformin on the scores obtained in different cognitive subtests that make up the Unified Huntington's Disease Rating Scale Baseline - Week 52 The tests that make up this subscale are the Symbol Digit Modalities Test.
It is a comparative test that is collected throughout the entire trial to assess the progression of cognitive functions in patients.
The test has 90 seconds time limit.
- Secondary Outcome Measures
Name Time Method Evaluate the effect of metformin on motor function in patients with Huntington's disease using the Unified Huntington's Disease Scale Total Motor Score. Baseline - Visit 1 (Week 0) - Week 26 - Week 52 The motor function evaluation will include the following exams:
Ocular Pursuit (horizontal and vertical), Saccade Initiation (horizontal and vertical), Saccade Velocity (horizontal and vertical), Dystrary, Lingual Protusion, Distonia (trunk and limbs), Korea (face , Mouth, trunk and extremities), Repulsion Test, Finger Tast (right and left), Pronate/ Supinate-Hands (right and left), Luria (palm test), Arm rigidity (right and left), Brady Kinesia-Body, Gait (walking difficulties), Tandem Walking.
The initial stage of Huntington's Disease is related to a score greater than 4 on the Unified Huntington's Disease Rating Scale Total Motor Score (UHDRS-TMS) and a total functional capacity (UHDRS-TFC) greater than 8.Evaluate the effect of metformin on functional capacity in patients with Huntington´s disease using Unified Huntington's Disease Scale Functional Capacity. Baseline - Visit 1 (Week 0) - Week 26 - Week 52 It is evaluated by means of a questionnaire on the following variables:
Occupation, Finance, Daily life activities, Domestic Works Level of Care.
The initial stage of Huntington's Disease is related to a score greater than 4 on the Unified Huntington's Disease Rating Scale Total Motor Score (UHDRS-TMS) and a total functional capacity (UHDRS-TFC) greater than 8.
Where 0 its de worse situation and 3 its normal situationEvaluate the effect of metformin on behavioral signs and symptoms in patients with Huntington´s disease using Problem Behaviors Assessment-Short form (PBA-s) Baseline - Visit 1 (Week 0) - Week 26 - Week 52 Specifically, will be evaluated on the changes in severity obtained in the items of depressed mood, suicidal ideation, anxiety, irritability, aggressiveness, apathy, persistent behavior and thinking, obsessive-compulsive behavior, delusional ideation, hallucinations, and disorientation.
The severity is scored is the 0 (absent) to 4 (severe; almost unbearable for the caregiver) The frequency is scored is the 0 (never / almost never) to 4 (daily / almost daily most of the day)Evaluate if there are genetic markers associated to metformin by analysis pharmacogenetic. Visit 1 (week 0) Analyze whether there are genetic markers associated with a better (or worse) response to metformin, through pharmacogenetics. The genotype of the patients will be analyzed on this material in a panel of single nucleotide polymorphisms (SNPs), related to the effect of Metformin and other medications that patients may be taking simultaneously.
Analyze the light chain protein of neurofilaments in peripheral blood. Visit 1 (week 0) and Visit 8 (Week 56) Analyze the light chain protein of neurofilaments in peripheral blood, as a circulating biomarker. Biomarker analysis will consist of obtaining information on the concentrations of various proteins, which tend to be released into the bloodstream when there are lesions in the nervous system.
Evaluate the effect of metformin in patients body with Huntington's disease. Baseline to Week 52 Incidence of adverse events and incidence of abnormal laboratory test results,
The classification of adverse events will be mild, moderate and serious by medical criteria.Evaluate the effect of metformin on the degree of independence in patients with Huntington's disease using the Unified Huntington's Disease Rating Scale Functional assessment and independence assessment. Baseline - Visit 1 (Week 0) - Week 26 - Week 52 The scale consists in two parts. The first part is to make a functional evaluation with scored is 0 or 1. The second part evaluate degree of independence with scored the 5% to 100%.
Trial Locations
- Locations (8)
Hospital General Universitario de Elche
🇪🇸Elche, Alicante, Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
Unitat Polivalent Barcelona Nord
🇪🇸Barcelona, Spain
Hospital Universitario Burgos
🇪🇸Burgos, Castilla Y León, Spain
Hospital Universitario y Politécnico La Fe
🇪🇸Valencia, València, Spain
Complejo Hospitalario de Albacete
🇪🇸Albacete, Castilla La Mancha, Spain
Hospital Universitario Central de Asturias
🇪🇸Oviedo, Principado De Asturias, Spain
Hospital Universitari Son Espases
🇪🇸Palma De Mallorca, Islas Baleares, Spain