TEsting METformin Against Cognitive Decline in HD

• Register: ClinicalTrials.gov
• Last refreshed on: 19 April 2022
• Main ID: NCT04826692
• Date of registration: 15/09/2020
• Prospective Registration: Yes
• Primary sponsor: Instituto de Investigacion Sanitaria La Fe
• Public title: TEsting METformin Against Cognitive Decline in HD
• Scientific title: "Randomized, Double-blind, Placebo-controlled Study to Assess the Effect of Metformin, an Activator of AMPK, on Cognitive Measures of Progression in Huntington's Disease Patients"
• Date of first enrolment: December 10, 2021
• Target sample size: 60
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/show/NCT04826692
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Spain

Contacts

• Name: Javier Mateo Lopez

• Name: Carmen Peiró, Phd, MD
• Affiliation: Instituto de Investigación Sanitaria La FE

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Symptomatic positive clinical diagnosis of Huntington disease.

2. Presence of 36 CAG repeats (or more) in the hunting gene based on centralized CAG
analysis.

3. Men or women between 21-65 years of age, inclusive, with an onset of HD at 18 years of
age or older.

4. 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.

5. A sum of > 4 points on the UHDRS-TMS scale and a diagnostic confidence level of 4.

6. Scale of independence = 75%.

7. Score on the UHDRS-TFC scale = 8 at the screening visit.

8. 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.

9. They must be trained and will require taking oral medication and will need to be
determined to comply with the specific study procedures.

10. 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.

11. 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.

Exclusion Criteria:

1. The participant has taken metformin in the last three months before the start of the
study.

2. The participant has diabetes of any kind.

3. The participant is pregnant or lactating.

4. The participant has a medical condition other than HD (metabolism, kidney function,
liver function, heart problems, etc.), or any contraindication against metformin.

5. The participant has an uncontrolled psychiatric condition.

6. Participant is allergic to metformin or any of the other ingredients of this medicine.

7. The participant has kidney problems [creatinine clearance <60 ml / min calculated
using Cockcroft-Gault formula] or liver problems.

8. The participant is dehydrated, from prolonged or severe diarrhea, or has vomited
several times.

9. The participant has a serious infection.

10. The participant has been treated for heart failure or has recently had a heart attack,
has severe circulation problems, or is having difficulty breathing.

11. The participant drinks> 6 units / day of alcohol (alcoholism).

12. Participants diagnosed with oncological disease.

13. Participants with a suicidal propensity, with an affirmative answer in items 4 or 5 in
the C-SSRS at the screening visit.



Age minimum: 21 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Huntington Disease

Intervention(s)

Drug: Metformin

Drug: Placebo

Primary Outcome(s)

Evaluate the effect of metformin on the scores obtained in different cognitive subtests that make up the Unified Huntington's Disease Rating Scale [Time Frame: Baseline - Week 52]

Evaluate the effect of metformin on the scores obtained in different cognitive subtests that make up the Unified Huntington's Disease Rating Scale (UHDRS). [Time Frame: Baseline - Week 52]

Secondary Outcome(s)

Evaluate the effect of metformin on motor function in patients with Huntington's disease using the Unified Huntington's Disease Scale Total Motor Score. [Time Frame: Baseline - Visit 1 (Week 0) - Week 26 - Week 52]

Evaluate the effect of metformin in patients body with Huntington's disease. [Time Frame: Baseline to Week 52]

Evaluate the effect of metformin on behavioral signs and symptoms in patients with Huntington´s disease using Problem Behaviors Assessment-Short form (PBA-s) [Time Frame: Baseline - Visit 1 (Week 0) - Week 26 - Week 52]

Evaluate the effect of metformin on functional capacity in patients with Huntington´s disease using Unified Huntington's Disease Scale Functional Capacity. [Time Frame: Baseline - Visit 1 (Week 0) - Week 26 - Week 52]

Evaluate if there are genetic markers associated to metformin by analysis pharmacogenetic. [Time Frame: Visit 1 (week 0)]

Analyze the light chain protein of neurofilaments in peripheral blood. [Time Frame: Visit 1 (week 0) and Visit 8 (Week 56)]

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. [Time Frame: Baseline - Visit 1 (Week 0) - Week 26 - Week 52]

Secondary ID(s)

TEMET-HD

Source(s) of Monetary Support

Please refer to primary and secondary sponsors