Effects of Nutritional Ketosis on Alcohol Metabolism

Before any study-related procedures are performed, you will be asked to read and sign this informed consent document. You will have an opportunity to ask questions before you sign the form and will be asked some questions by the study personnel to confirm your understanding. You will be asked not to drink before this and all other visits. The screening visit may occur on one or more visits. The study visit(s) will occur at the CSA (Center for Studies of Addiction), PCAM 4-215 (Perlman Center for Advanced Medicine, 3400 Civic Center Blvd) facilities, HUP Dulles 116 (Hospital of the University of Pennsylvania, 3400 Spruce St.) and/or Stellar Chance Laboratories (440 Curie Blvd.) Before the consent and all lab visits, study staff will check your BrAC using a Breathalyzer to ensure that you are able to complete the visit. Your BrAC must be 0.000% to complete this visit.

  Table 1. Study Visits

Consent and Screening Session (approximately 4 hrs).
The following will occur at this visit. The visit may be completed on more than one day at the CSA following signed consent:

• First, we will ask you to show us a legal photo ID and then undergo a breathalyzer test to ensure that you are able to make a well-reasoned decision about whether or not to participate in the study. Your BrAC must be 0.000% to complete this visit.
• We will ask you to provide some demographic information, including your current address to register you as a patient at the University of Pennsylvania, if you have not been a patient here before.
• A clinician will ask you questions about your medical history and perform a physical examination. Study staff trained in drawing blood will draw a total of approximately 3 tablespoons (44 mL) of blood for standard laboratory tests and genetic analysis. It is possible that your bloodwork will need to be repeated due to unforeseen events (abnormal findings or potential lab errors).
• Study staff will also ask you to provide a urine sample for routine urinalysis, drug screen, ketone levels, and a pregnancy test if you are a woman who is able to become pregnant.   If you are pregnant, breast-feeding, or if you test positive for certain drugs, you will not be eligible for the study.
• Study personnel will measure your vital signs (blood pressure and pulse), weight, and height and ask you about any medications, recreational drugs or supplements you may be taking.
• A clinician will do a brief physical exam and ask questions about your current and past medical history.
• Study personnel will complete a brief psychiatric interview and ask you about your alcohol and cigarette use over the past 90 days.
• You must complete a screening evaluation form in advance of the MRI exam for the presence of medical implants or other foreign bodies that could pose an injury when undergoing MRI. The screening is only as effective as the provided medical history. In cases where there is insufficient information to evaluate the risks associated with an implant or foreign body, the MRI study will not be allowed to proceed. 

After your screening visit is complete, we will call you within 5 business days to confirm whether you are eligible to continue with the study and schedule you for the rest of your study visits.

Dietary Intervention (4 weeks each)
You will be asked to adhere to a 4-weeks ketogenic diet. Depending on scheduling availability, we may ask you to remain on the diet until the final lab visit. This would be no more than an additional 3 days, and we will provide you with the additional meals. The meals will be provided by a commercial meal service (Factor75) and they will deliver the meals to to your residence weekly. We ask that you just to eat the food provided to you for the 4-weeks you are in the study. Your compliance to the dietary intervention will be assessed daily with a urine ketone levels test that you will be asked to perform each morning and send us a picture of the test by text or email. We will also check your blood ketone levels on the days of the lab visits. Each week a staff member will call you to check on your health and wellbeing, make sure you are receiving your study meals and record the amounts of each meal you consumed during the week. Staff will also ask you some questions about your mood and record your alcohol use for the week. We will also ask you about your adherence to the diet during the study visits.  

Study lab visits lab 1 and 3 (week 4; approximately 8 hrs. each)
Staff will call you the night before to reminder you not to eat or drink anything except water after midnight the day before and on the day of the study visit. We will provide breakfast and lunch. Staff will review the current list medications and vitamins you provided at the screening visit, and we will ask if anything has changed. 
We will setup a Lyft ride to bring you to Stellar Chance Laboratories (440 Curie Blvd.).

On the day of the study lab visits, the following will occur:

• We will provide you with a light meal after we record your BrAC (must be 0.000% to continue), finger stick for blood glucose level, and vital signs. You will be asked about your recent use of drugs, alcohol, and nicotine. You will be asked to provide a urine sample to conduct a drug screen, urine ketone level, and a pregnancy test (if you are a woman able to become pregnant).
• You will receive a brain 7-Tesla MRI scan (~1.5 hour). An MRI is a type of scan that uses radio waves to take detailed pictures of the body. You will be asked to lie on an MRI table where the technologist will place a receiver on the part of your body to be studied (brain). You will be provided a blanket for comfort and earplugs since the MRI makes noises while it is scanning. You will still be able to hear some sound to ensure you can communicate with the technologist and can follow any direction given throughout the MRI scan. The technologist will slowly slide you into the MRI magnet where radio waves will be transmitted into you.
  • You will be asked to fill out an MRI safety form.
  • You will be asked to remove any metal you may be wearing.
  • We will provide you with earplugs for the noise from the MRI scanner, and you will be positioned on the imaging table with your head in the scanner, held comfortably in a special head holder. 
    You will be instructed not to move your head and to lie as still as you can during the scan (~ 90 minutes). You will undergo several scans, during which we will obtain a structure image of your brain, NAD (a cofactor involved in energy metabolism), lactate (a byproduct of energy metabolism) and neurotransmitter GABA and glutamate.
• We will travel to 3535 Market St. for the reminder of the laboratory visit.
• Blood sample will be collected, and lunch will be provided.
• A dose of alcohol calculated to elevate breath alcohol concentration to approximately 0.08% will be provided. We will measure alcohol intoxication prior to and at pre-specified times following alcohol administration using the following measurements: breath alcohol concentration, motor (groove pegboard task) and cognitive (go-no-go task) tests, and questionnaires. Study personnel may ask about side effects that you may be feeling through the laboratory procedures. Please let us know if you are feeling anything different. During the alcohol challenge, you will be free to read or watch videos.
• At the end of the laboratory procedures, we will provide a snack and measure your blood glucose and ketone levels to make sure you are safe to go home by Lyft. We will ask again about any side effects, and we will set up the next lab visit.

Study lab visit 2 (week 2; approximately 5 hrs.)
Staff will call you the day before to reminder you not to drink alcohol after 10pm the night before and set up your Lyft ride to to 3535 Market St. We ask that you eat breakfast at your normal time in the morning at home.Staff will review the current list medications and vitamins you provided at the last study visit, and we will ask if anything has changed.

On the day of the study lab visits, the following will occur:

• We will record your BrAC (must be 0.000% to continue), finger stick for blood glucose level, and vital signs. You will be asked about your recent use of drugs, alcohol, and nicotine. You will be asked to provide a urine sample to conduct a drug screen, urine ketone level, and a pregnancy test (if you are a woman able to become pregnant).
• Blood sample will be collected, and lunch will be provided.
• A dose of alcohol calculated to elevate breath alcohol concentration to approximately 0.08% will be provided. We will measure alcohol intoxication prior to and at pre-specified times following alcohol administration using the following measurements: breath alcohol concentration, motor (groove pegboard task) and cognitive (go-no-go task) tests, and questionnaires. Study personnel may ask about side effects that you may be feeling through the laboratory procedures. Please let us know if you are feeling anything different. During the alcohol challenge, you will be free to read or watch videos.
• At the end of the laboratory procedures, we will provide a snack and measure your blood glucose and ketone levels to make sure you are safe to go home via Lyft. We will ask again about any side effects, and we will set up the next lab visit approximately 2 weeks away.